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Resumen Las enfermedades neurodegenerativas (ND) se caracterizan por la pérdida de función y muerte neuronal progresiva y cuestan aproximadamente el 12% del PIB de Colombia en 2020 anual ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1002/ana.24897","ISSN":"15318249","PMID":"28198092","author":[{"dropping-particle":"","family":"Gooch","given":"Clifton L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pracht","given":"Etienne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Borenstein","given":"Amy R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Annals of Neurology","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2017"]]},"page":"479-484","title":"The burden of neurological disease in the United States: A summary report and call to action","type":"article-journal","volume":"81"},"uris":["http://www.mendeley.com/documents/?uuid=b92e8dd8-4803-4617-bcef-793fc241be2b"]}],"mendeley":{"formattedCitation":"(Gooch et al., 2017)","plainTextFormattedCitation":"(Gooch et al., 2017)","previouslyFormattedCitation":"[1]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Gooch et al., 2017), la prevalencia de demencia es la quinta del continente ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S1474-4422(18)30403-4","ISSN":"14744465","PMID":"30497964","abstract":"Background: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists. Methods: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugar-sweetened beverages). Findings: In 2016, the global number of individuals who lived with dementia was 43·8 million (95% uncertainty interval [UI] 37·8–51·0), increased from 20.2 million (17·4–23·5) in 1990. This increase of 117% (95% UI 114–121) contrasted with a minor increase in age-standardised prevalence of 1·7% (1·0–2·4), from 701 cases (95% UI 602–815) per 100 000 population in 1990 to 712 cases (614–828) per 100 000 population in 2016. More women than men had dementia in 2016 (27·0 million, 95% UI 23·3–31·4, vs 16.8 million, 14.4–19.6), and dementia was the fifth leading cause of death globally, accounting for 2·4 million (95% UI 2·1–2·8) deaths. Overall, 28·8 million (95% UI 24·5–34·0) DALYs were attributed to dementia; 6·4 million (95% UI 3·4–10·5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sug…","author":[{"dropping-particle":"","family":"Nichols","given":"Emma","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Szoeke","given":"Cassandra E.I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vollset","given":"Stein 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poblacional a 2050 ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"abstract":"Este documento, consolida y describe un conjunto de indicadores trazadores sobre el envejecimiento demográfico del país para el periodo 2005-2020, con el propósito de instrumentalizar criterios de focalización que sirvan para la asignación de recursos no solo a las demandas actuales para la atención de las personas mayores, sino también a las previsiones necesarias en materia de bienestar social, derivadas del envejecimiento progresivo de la población.","author":[{"dropping-particle":"","family":"MINSALUD","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["2013"]]},"number-of-pages":"48","publisher-place":"Bogotá, Colombia","title":"Envejecimiento demográfico. Colombia 1951-2020 dinámica demográfica y estructuras poblacionales","type":"report"},"uris":["http://www.mendeley.com/documents/?uuid=6eb98b3f-e3af-48fe-abd2-ddcee526a372"]}],"mendeley":{"formattedCitation":"(MINSALUD, 2013)","plainTextFormattedCitation":"(MINSALUD, 2013)","previouslyFormattedCitation":"[3]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(MINSALUD, 2013). Dentro de los factores que dificultan el tratamiento de ND se encuentran una baja precisión diagnóstica, el diagnostico tardío ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/s41591-021-01382-x","ISSN":"1546-170X","abstract":"T he prevalence of neurodegenerative diseases is expected to rise with the increasing life expectancy in most countries. About 50 million people are currently affected by dementia 1 , which is estimated to increase to 130 million by 2050 (ref. 2). Dementia is a major cause of disability, institutionalization and mortality, and the global cost is US$ 1 trillion 2. Alzheimer's disease (AD) is the most common neurodegenerative disease and accounts for 60-70% of all dementia cases. Twenty percent of women and 10% of men will develop AD 3. Affected individuals typically develop episodic memory impairment followed by other cognitive symptoms, including difficulties with language, difficulties with executive and visuospa-tial functions and, ultimately, dementia. Symptomatic treatment with acetylcholinesterase inhibitors can improve cognition but does not halt the underlying disease progression. In AD, amyloid-β (Aβ) starts to aggregate and accumulate in cortical extracellular plaques ~10-30 years before dementia onset (Box 1) 4-6. Other key pathological features of AD include neuronal neurofibrillary tangles and neu-ropil threads containing hyperphosphorylated tau. Tau-containing tangles restricted to the medial temporal lobe are found in most healthy people older than 60 years (Box 1) 7. However, in AD, tau aggregates spread from the medial temporal lobe and build up in larger quantities throughout the neocortex in a stereotypic pattern (Fig. 1b) 8,9. This process is probably driven, or at least facilitated, by Aβ pathology 10,11. Autosomal dominant forms of AD are all caused by mutations in genes encoding Aβ turnover-related proteins, which promote Aβ aggregation, resulting in widespread tau-tangle pathology and cognitive impairment 12. Tau aggregates that are different in structure, and not related to Aβ pathology, are observed in other neurodegenerative diseases, including progressive supra-nuclear palsy (PSP), corticobasal degeneration (CBD) and a variant of frontotemporal dementia (FTD) called Pick's disease (Box 1) 13. Parkinson's disease (PD) is the second-most common neurode-generative disorder, with a global prevalence of over 6 million 1. It is a movement disorder characterized by bradykinesia, muscular rigidity, resting tremor and postural and gait impairment. Many of these symptoms are related to loss of dopamine-producing neurons in the substantia nigra pars compacta, and particularly bradyki-nesia and rigidity initially respond well to symptomat…","author":[{"dropping-particle":"","family":"Hansson","given":"Oskar","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Medicine","id":"ITEM-1","issue":"June","issued":{"date-parts":[["2021"]]},"publisher":"Springer US","title":"Biomarkers for neurodegenerative diseases","type":"article-journal","volume":"27"},"uris":["http://www.mendeley.com/documents/?uuid=5d37123f-8d83-4ee9-8427-f4e44070c306"]}],"mendeley":{"formattedCitation":"(Hansson, 2021)","plainTextFormattedCitation":"(Hansson, 2021)","previouslyFormattedCitation":"[4]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Hansson, 2021) y una alta tasa de fallo terapéutico ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/alzrt269","ISSN":"17589193","abstract":"Introduction. Alzheimer's disease (AD) is increasing in frequency as the global population ages. Five drugs are approved for treatment of AD, including four cholinesterase inhibitors and an N-methyl-D-aspartate (NMDA)-receptor antagonist. We have an urgent need to find new therapies for AD. Methods. We examined Clinicaltrials.gov, a public website that records ongoing clinical trials. We examined the decade of 2002 to 2012, to better understand AD-drug development. We reviewed trials by sponsor, sites, drug mechanism of action, duration, number of patients required, and rate of success in terms of advancement from one phase to the next. We also reviewed the current AD therapy pipeline. Results: During the 2002 to 2012 observation period, 413 AD trials were performed: 124 Phase 1 trials, 206 Phase 2 trials, and 83 Phase 3 trials. Seventy-eight percent were sponsored by pharmaceutical companies. The United States of America (U.S.) remains the single world region with the greatest number of trials; cumulatively, more non-U.S. than U.S. trials are performed. The largest number of registered trials addressed symptomatic agents aimed at improving cognition (36.6%), followed by trials of disease-modifying small molecules (35.1%) and trials of disease-modifying immunotherapies (18%). The mean length of trials increases from Phase 2 to Phase 3, and the number of participants in trials increases between Phase 2 and Phase 3. Trials of disease-modifying agents are larger and longer than those for symptomatic agents. A very high attrition rate was found, with an overall success rate during the 2002 to 2012 period of 0.4% (99.6% failure). Conclusions: The Clinicaltrials.gov database demonstrates that relatively few clinical trials are undertaken for AD therapeutics, considering the magnitude of the problem. The success rate for advancing from one phase to another is low, and the number of compounds progressing to regulatory review is among the lowest found in any therapeutic area. The AD drug-development ecosystem requires support. © 2014 Cummings et al.; licensee BioMed Central Ltd.","author":[{"dropping-particle":"","family":"Cummings","given":"Jeffrey L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morstorf","given":"Travis","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhong","given":"Kate","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Alzheimer's Research and Therapy","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2014"]]},"page":"1-7","title":"Alzheimer's disease drug-development pipeline: Few candidates, frequent failures","type":"article-journal","volume":"6"},"uris":["http://www.mendeley.com/documents/?uuid=89ad19b0-4563-4098-8c49-42b995bdc037"]}],"mendeley":{"formattedCitation":"(Cummings et al., 2014)","plainTextFormattedCitation":"(Cummings et al., 2014)","previouslyFormattedCitation":"[5]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Cummings et al., 2014), por lo cual, se necesitan biomarcadores y blancos para ND. Una de las células gliales cuya disfunción ha sido implicada en la patogénesis y curso de ND es el astrocito ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/brain/awz260","author":[{"dropping-particle":"","family":"Wilson","given":"Heather","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dervenoulas","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pagano","given":"Gennaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tyacke","given":"Robin J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Polychronis","given":"Sotirios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Myers","given":"Jim","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gunn","given":"Roger N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rabiner","given":"Eugenii A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nutt","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Brain","id":"ITEM-1","issued":{"date-parts":[["2019"]]},"page":"3116-3128","title":"Imidazoline 2 binding sites reflecting astroglia pathology in Parkinson’s disease: an in vivo 11C-BU99008 PET study","type":"article-journal","volume":"142"},"uris":["http://www.mendeley.com/documents/?uuid=5ddeb131-102e-4023-84c2-20441a2956cf"]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/J.TINS.2017.04.001","ISSN":"1878108X","PMID":"28527591","abstract":"Astrocytes are the most populous glial subtype and are critical for brain function. Despite this, historically there have been few studies into the role that they may have in neurodegenerative diseases, such as Parkinson's disease (PD). Recently, however, several studies have determined that genes known to have a causative role in the development of PD are expressed in astrocytes and have important roles in astrocyte function. Here, we review these recent developments and discuss their impact on our understanding of the pathophysiology of PD, and the implications that this might have for its treatment.","author":[{"dropping-particle":"","family":"Booth","given":"Heather D.E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hirst","given":"Warren D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wade-Martins","given":"Richard","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Trends in Neurosciences","id":"ITEM-2","issue":"6","issued":{"date-parts":[["2017","6","1"]]},"page":"358","publisher":"Elsevier","title":"The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis","type":"article-journal","volume":"40"},"uris":["http://www.mendeley.com/documents/?uuid=1afbe873-b9ad-3057-8bc5-cd118544fbbf"]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/JNC.14273","ISSN":"1471-4159","PMID":"29222909","abstract":"Vascular contributions to cognitive impairment and dementia (VCID) is understood to be the second most common cause of dementia after Alzheimer's disease, and is also a frequent comorbidity with Alzheimer's disease. While VCID is widely acknowledged as a key contributor to dementia, the mechanistic underpinnings of VCID remain poorly understood. In this review, we address the potential role of astrocytes in the pathophysiology of VCID. The vast majority of the blood vessels in the brain are surrounded by astrocytic end-feet. Given that astrocytes make up a significant proportion of the cells in the brain, and that astrocytes are usually passively connected to one another through gap junctions, we hypothesize that astrocytes are key mediators of cognitive impairment because of cerebrovascular disease. In this review, we discuss the existing body of literature regarding the role of astrocytes at the vasculature in the brain, and the known consequences of their dysfunction, as well as our hypotheses regarding the role astrocytes play in VCID. (Figure presented.). This article is part of the Special Issue “Vascular Dementia”.","author":[{"dropping-particle":"","family":"Price","given":"Brittani R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Norris","given":"Christopher M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sompol","given":"Pradoldej","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilcock","given":"Donna M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of neurochemistry","id":"ITEM-3","issue":"5","issued":{"date-parts":[["2018","3","1"]]},"page":"644-650","publisher":"J Neurochem","title":"An emerging role of astrocytes in vascular contributions to cognitive impairment and dementia","type":"article-journal","volume":"144"},"uris":["http://www.mendeley.com/documents/?uuid=cc1d0760-ce26-3b52-ad03-16f15899afd0"]},{"id":"ITEM-4","itemData":{"DOI":"10.1007/s00401-015-1513-1","ISSN":"14320533","PMID":"26671410","abstract":"The neurone-centred view of the past disregarded or downplayed the role of astroglia as a primary component in the pathogenesis of neurological diseases. As this concept is changing, so is also the perceived role of astrocytes in the healthy and diseased brain and spinal cord. We have started to unravel the different signalling mechanisms that trigger specific molecular, morphological and functional changes in reactive astrocytes that are critical for repairing tissue and maintaining function in CNS pathologies, such as neurotrauma, stroke, or neurodegenerative diseases. An increasing body of evidence shows that the effects of astrogliosis on the neural tissue and its functions are not uniform or stereotypic, but vary in a context-specific manner from astrogliosis being an adaptive beneficial response under some circumstances to a maladaptive and deleterious process in another context. There is a growing support for the concept of astrocytopathies in which the disruption of normal astrocyte functions, astrodegeneration or dysfunctional/maladaptive astrogliosis are the primary cause or the main factor in neurological dysfunction and disease. This review describes the multiple roles of astrocytes in the healthy CNS, discusses the diversity of astroglial responses in neurological disorders and argues that targeting astrocytes may represent an effective therapeutic strategy for Alexander disease, neurotrauma, stroke, epilepsy and Alzheimer’s disease as well as other neurodegenerative diseases.","author":[{"dropping-particle":"","family":"Pekny","given":"Milos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pekna","given":"Marcela","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Messing","given":"Albee","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Steinhäuser","given":"Christian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Jin Moo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parpura","given":"Vladimir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hol","given":"Elly M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"V.","family":"Sofroniew","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Verkhratsky","given":"Alexei","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Acta Neuropathologica","id":"ITEM-4","issue":"3","issued":{"date-parts":[["2016"]]},"page":"323-345","publisher":"Springer Berlin Heidelberg","title":"Astrocytes: a central element in neurological diseases","type":"article-journal","volume":"131"},"uris":["http://www.mendeley.com/documents/?uuid=be53e52b-97a8-44a6-ae90-fae93d0a322f"]}],"mendeley":{"formattedCitation":"(Booth et al., 2017; Pekny et al., 2016; Price et al., 2018; Wilson et al., 2019)","plainTextFormattedCitation":"(Booth et al., 2017; Pekny et al., 2016; Price et al., 2018; Wilson et al., 2019)","previouslyFormattedCitation":"[6]–[9]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Booth et al., 2017; Pekny et al., 2016; Price et al., 2018; Wilson et al., 2019), cuya actividad es esencial para la neurona brindando soporte metabólico en la sinapsis y la unidad neurovascular ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cmet.2011.08.016","ISSN":"15504131","PMID":"22152301","abstract":"The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes - a type of glial cell - have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a \"neurocentric\" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes. © 2011 Elsevier Inc.","author":[{"dropping-particle":"","family":"Bélanger","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Allaman","given":"Igor","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Magistretti","given":"Pierre J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cell Metabolism","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2011"]]},"page":"724-738","title":"Brain energy metabolism: Focus on Astrocyte-neuron metabolic cooperation","type":"article-journal","volume":"14"},"uris":["http://www.mendeley.com/documents/?uuid=db3592e0-bd4d-4509-9358-60e0b6840d0f"]}],"mendeley":{"formattedCitation":"(Bélanger et al., 2011)","plainTextFormattedCitation":"(Bélanger et al., 2011)","previouslyFormattedCitation":"[10]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Bélanger et al., 2011). A nivel extracelular, firmas de ARN cortos no-codificantes (sncRNA) han sido empleadas con relativo éxito para el diagnóstico de las principales ND ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1212/WNL.0000000000004844","ISBN":"0000000000","ISSN":"1526632X","PMID":"29282329","abstract":"Objective To investigate the feasibility of microRNA (miRNA) levels in CSF as biomarkers for prodromal Huntington disease (HD). Methods miRNA levels were measured in CSF from 60 PREDICT-HD study participants using the HTG protocol. Using a CAG-Age Product score, 30 prodromal HD participants were selected based on estimated probability of imminent clinical diagnosis of HD (i.e., low, medium, high; n = 10/ group). For comparison, participants already diagnosed (n = 15) and healthy controls (n = 15) were also selected. Results A total of 2,081 miRNAs were detected and 6 were significantly increased in the prodromal HD gene expansion carriers vs controls at false discovery rate q < 0.05 (miR-520f-3p, miR-135b-3p, miR-4317, miR-3928-5p, miR-8082, miR-140-5p). Evaluating the miRNA levels in each of the HD risk categories, all 6 revealed a pattern of increasing abundance from control to low risk, and from low risk to medium risk, which then leveled off from the medium to high risk and HD diagnosed groups. Conclusions This study reports miRNAs as CSF biomarkers of prodromal and diagnosed HD. Importantly, miRNAs were detected in the prodromal HD groups furthest from diagnosis where treatments are likely to be most consequential and meaningful. The identification of potential biomarkers in the disease prodrome may prove useful in evaluating treatments that may postpone disease onset. Clinicaltrials.gov identifier NCT00051324.","author":[{"dropping-particle":"","family":"Reed","given":"Eric R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Latourelle","given":"Jeanne C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bockholt","given":"Jeremy H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bregu","given":"Joli","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Smock","given":"Justin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Paulsen","given":"Jane S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Myers","given":"Richard H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Neurology","id":"ITEM-1","issue":"8","issued":{"date-parts":[["2018"]]},"page":"E264-E272","title":"MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study","type":"article-journal","volume":"90"},"uris":["http://www.mendeley.com/documents/?uuid=a9015075-4bcc-472b-8b24-bac3fb0c1bb5"]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/s41398-019-0579-2","ISBN":"4139801905","ISSN":"21583188","PMID":"31591382","abstract":"Alzheimer’s disease (AD) is the most common neurodegenerative disorder causing huge emotional and economic burden to our societies. An effective therapy has not been implicated yet, which is in part also due to the fact that pathological changes occur years before clinical symptoms manifest. Thus, there is a great need for the development of a translatable biomarker. Recent evidence highlights microRNAs as candidate biomarkers. In this study, we use next-generation sequencing to study the small noncoding RNAome (sncRNAome) in exosomes derived from human cerebrospinal fluid (CSF). We show that the sncRNAome from CSF-derived exosomes is dominated not only by microRNAs (miRNAs) but also by PIWI-interacting RNAs (piRNAs). We define a combined signature consisting of three miRNAs and three piRNAs that are suitable to detect AD with an AUC of 0.83 in a replication cohort and furthermore predict the conversion of mild–cognitive impaired (MCI) patients to AD dementia with an AUC of 0.86 for the piRNA signature. When combining the smallRNA signature with pTau and Aβ 42/40 ratio the AUC reaches 0.98. Our study reports a novel exosomal small noncoding RNA signature to detect AD pathology and provides the first evidence that in addition to miRNAs, piRNAs should also be considered as a candidate biomarker for AD.","author":[{"dropping-particle":"","family":"Jain","given":"Gaurav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stuendl","given":"Anne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rao","given":"Pooja","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berulava","given":"Tea","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pena Centeno","given":"Tonatiuh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaurani","given":"Lalit","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burkhardt","given":"Susanne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Delalle","given":"Ivana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kornhuber","given":"Johannes","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hüll","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maier","given":"Wolfgang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Peters","given":"Oliver","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Esselmann","given":"Hermann","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schulte","given":"Claudia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Deuschle","given":"Christian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Synofzik","given":"Mathis","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wiltfang","given":"Jens","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mollenhauer","given":"Brit","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maetzler","given":"Walter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schneider","given":"Anja","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fischer","given":"Andre","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Translational Psychiatry","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2019"]]},"publisher":"Springer US","title":"A combined miRNA–piRNA signature to detect Alzheimer’s disease","type":"article-journal","volume":"9"},"uris":["http://www.mendeley.com/documents/?uuid=33af8cb6-e05c-4217-9293-5258ee4425b1"]},{"id":"ITEM-3","itemData":{"DOI":"10.1038/s41598-017-14301-3","ISSN":"20452322","PMID":"29084979","abstract":"Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is currently no single definitive test for MS. Circulating exosomes represent promising candidate biomarkers for a host of human diseases. Exosomes contain RNA, DNA, and proteins, can cross the blood-brain barrier, and are secreted from almost all cell types including cells of the CNS. We hypothesized that serum exosomal miRNAs could present a useful blood-based assay for MS disease detection and monitoring. Exosome-associated microRNAs in serum samples from MS patients (n = 25) and matched healthy controls (n = 11) were profiled using small RNA next generation sequencing. We identified differentially expressed exosomal miRNAs in both relapsing-remitting MS (RRMS) (miR-15b-5p, miR-451a, miR-30b-5p, miR-342-3p) and progressive MS patient sera (miR-127-3p, miR-370-3p, miR-409-3p, miR-432-5p) in relation to controls. Critically, we identified a group of nine miRNAs (miR-15b-5p, miR-23a-3p, miR-223-3p, miR-374a-5p, miR-30b-5p, miR-433-3p, miR-485-3p, miR-342-3p, miR-432-5p) that distinguished relapsing-remitting from progressive disease. Eight out of nine miRNAs were validated in an independent group (n = 11) of progressive MS cases. This is the first demonstration that microRNAs associated with circulating exosomes are informative biomarkers not only for the diagnosis of MS, but in predicting disease subtype with a high degree of accuracy.","author":[{"dropping-particle":"","family":"Ebrahimkhani","given":"Saeideh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vafaee","given":"Fatemeh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Young","given":"Paul E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hur","given":"Suzy S.J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hawke","given":"Simon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Devenney","given":"Emma","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beadnall","given":"Heidi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barnett","given":"Michael H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Catherine M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Buckland","given":"Michael E","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2017"]]},"title":"Exosomal microRNA signatures in multiple sclerosis reflect disease status","type":"article-journal","volume":"7"},"uris":["http://www.mendeley.com/documents/?uuid=5ac1461c-b084-31dc-b269-9087140ed6ed"]},{"id":"ITEM-4","itemData":{"author":[{"dropping-particle":"","family":"Cristina","given":"Marcia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Santos","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barreto-sanz","given":"Miguel Arturo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"S","given":"Bruna Renata","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bell","given":"Rosie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Widnall","given":"Catherine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Perez","given":"Luis Tosar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berteau","given":"Caroline","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schulte","given":"Claudia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scheller","given":"Dieter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berg","given":"Daniela","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maetzler","given":"Walter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pedro","given":"A F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nogueira","given":"Andre","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-4","issue":"25","issued":{"date-parts":[["2018"]]},"page":"17455-17465","title":"miRNA-based signatures in cerebrospinal fluid as potential diagnostic tools for early stage Parkinson’s disease","type":"article-journal","volume":"9"},"uris":["http://www.mendeley.com/documents/?uuid=74905ce3-e323-4671-b829-f5cf1d9f6654"]}],"mendeley":{"formattedCitation":"(Cristina et al., 2018; Ebrahimkhani et al., 2017; Jain et al., 2019; Reed et al., 2018)","plainTextFormattedCitation":"(Cristina et al., 2018; Ebrahimkhani et al., 2017; Jain et al., 2019; Reed et al., 2018)","previouslyFormattedCitation":"[11]–[14]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Cristina et al., 2018; Ebrahimkhani et al., 2017; Jain et al., 2019; Reed et al., 2018), por lo que, su estudio a nivel astrocitario se considera relevante para el diseño de biomarcadores y blancos terapéuticos puesto que la integración de datos transcriptómicos ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3389/fncel.2014.00047","ISSN":"16625102","abstract":"The human brain is one of the most complex biological systems, and the cognitive abilities have greatly expanded compared to invertebrates without much expansion in the number of protein coding genes. This suggests that gene regulation plays a very important role in the development and function of nervous system, by acting at multiple levels such as transcription and translation. In this article we discuss the regulatory roles of three classes of non-protein coding RNAs (ncRNAs)-microRNAs (miRNAs), piwi-interacting RNA (piRNAs) and long-non-coding RNA (lncRNA), in the process of neurogenesis and nervous function including control of synaptic plasticity and potential roles in neurodegenerative diseases. miRNAs are involved in diverse processes including neurogenesis where they channelize the cellular physiology toward neuronal differentiation. miRNAs can also indirectly influence neurogenesis by regulating the proliferation and self renewal of neural stem cells and are dysregulated in several neurodegenerative diseases. miRNAs are also known to regulate synaptic plasticity and are usually found to be co-expressed with their targets. The dynamics of gene regulation is thus dependent on the local architecture of the gene regulatory network (GRN) around the miRNA and its targets. piRNAs had been classically known to regulate transposons in the germ cells. However, piRNAs have been, recently, found to be expressed in the brain and possibly function by imparting epigenetic changes by DNA methylation. piRNAs are known to be maternally inherited and we assume that they may play a role in early development. We also explore the possible function of piRNAs in regulating the expansion of transposons in the brain. Brain is known to express several lncRNA but functional roles in brain development are attributed to a few lncRNA while functions of most of the them remain unknown. We review the roles of some known lncRNA and explore the other possible functions of lncRNAs including their interaction with miRNAs. © 2014 Iyengar, Choudhary, Sarangdhar, Venkatesh, Gadgil and Pillai.","author":[{"dropping-particle":"","family":"Iyengar","given":"Bharat R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Choudhary","given":"Ashwani","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sarangdhar","given":"Mayuresh A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"V.","family":"Venkatesh","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gadgil","given":"Chetan J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillai","given":"Beena","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Frontiers in Cellular Neuroscience","id":"ITEM-1","issue":"FEB","issued":{"date-parts":[["2014"]]},"page":"1-10","title":"Non-coding RNA interact to regulate neuronal development and function","type":"article-journal","volume":"8"},"uris":["http://www.mendeley.com/documents/?uuid=c0ab22c0-30fe-4391-84c0-510aef3fce9e"]}],"mendeley":{"formattedCitation":"(Iyengar et al., 2014)","plainTextFormattedCitation":"(Iyengar et al., 2014)","previouslyFormattedCitation":"[15]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Iyengar et al., 2014), a Modelos Metabólicos a Escala Genómicas (GEM), incrementa la precisión de estos para la predicción ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/978-3-319-98758-3_5/FIGURES/4","ISSN":"22148019","PMID":"30382569","abstract":"This chapter introduces different aspects of bioinformatics with a brief discussion in the systems biology context. Example applications in network pharmacology of traditional Chinese medicine, systems metabolic engineering, and plant genome-scale modelling are described. Lastly, this chapter concludes on how bioinformatics helps to integrate omics data derived from various studies described in previous chapters for a holistic understanding of secondary metabolite production in P. minus.","author":[{"dropping-particle":"","family":"Goh","given":"Hoe Han","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Advances in Experimental Medicine and Biology","id":"ITEM-1","issued":{"date-parts":[["2018"]]},"page":"69-80","publisher":"Springer New York LLC","title":"Integrative multi-omics through bioinformatics","type":"article-journal","volume":"1102"},"uris":["http://www.mendeley.com/documents/?uuid=15095f40-488a-39aa-b700-9c4aeb331e53"]},{"id":"ITEM-2","itemData":{"DOI":"10.1177/0193945917697223","ISSN":"1552-8456","PMID":"28303750","abstract":"The microbes residing in the human gut, referred to as the microbiome, are intricately linked to energy homeostasis and subsequently obesity. Integral to the origins of obesity, the microbiome is believed to affect not only health of the human gut but also overall health. This microbiome-obesity association is mediated through the process of energy extraction, metabolism, and cross talk between the brain and the gut microbiome. Host exposures, including diet, that potentially modify genetic predisposition to obesity and affect weight management are reviewed. The higher prevalence of obesity among women and recent evidence linking obesity during pregnancy with offspring health make this topic particularly relevant. Current limitations in microbiome research to address obesity and future advances in this field are described. Applications of this science with respect to applied nursing and overall health care in general are included, with emphasis on the reproductive health of women and their offspring.","author":[{"dropping-particle":"","family":"Basler","given":"Georg","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nikoloski","given":"Zoran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Larhlimi","given":"Abdelhalim","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barabási","given":"Albert-lászló","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-2","issued":{"date-parts":[["2016"]]},"page":"956-968","title":"Control of Fluxes in Metabolic Networks Authors : Contact information : Running title : Keywords :","type":"article-journal"},"uris":["http://www.mendeley.com/documents/?uuid=862840ce-8f3a-494c-a612-e15645704642"]}],"mendeley":{"formattedCitation":"(Basler et al., 2016; Goh, 2018)","plainTextFormattedCitation":"(Basler et al., 2016; Goh, 2018)","previouslyFormattedCitation":"[16],[17]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Basler et al., 2016; Goh, 2018). Dentro de los factores que alteran la función astrocitaria ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/jne.12768","ISSN":"13652826","PMID":"31278797","abstract":"Although it has been shown that telomerase has neuroprotective effects, mainly as a result of its non-canonical functions in neuronal cells, its role with respect to glial cells remains unknown. There is growing evidence indicating that telomerase plays an important role with respect to inflammation, especially in the regulation of pro-inflammatory cytokine gene expression. The present study aimed to evaluate the role of telomerase in an astrocyte cell model treated with palmitic acid (PA) and tibolone. Cell death, reactive oxygen species production and interleukin-6 expression were evaluated under telomerase inhibition with the BIBR1532 compound in T98G cells treated with tibolone and PA, using fluorometry, flow cytometry, enzyme-linked immunosorbent assays and the quantitative polymerase chain reaction. The results obtained showed that telomerase protein was increased by PA after 36 hours, alone or in combination with tibolone, and that its activity was affected by PA. Telomerase inhibition reduced interleukin-6 expression and it interfered with the protective effects of tibolone on cell death. Moreover, tibolone increased Tyr707 phosphorylation in PA-treated cells. In the present study, we provide novel findings about the regulation of telomerase by PA and tibolone. Telomerase was involved in inflammation by PA and in protective effects of tibolone. Therefore, we conclude that telomerase could play a dual role in these cells.","author":[{"dropping-particle":"","family":"González-Giraldo","given":"Yeimy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"V.","family":"Garzón-Benitez","given":"Angie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Forero","given":"Diego A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barreto","given":"George E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Neuroendocrinology","id":"ITEM-1","issue":"8","issued":{"date-parts":[["2019","8","23"]]},"publisher":"Blackwell Publishing Ltd","title":"TERT inhibition leads to reduction of IL-6 expression induced by palmitic acid and interferes with the protective effects of tibolone in an astrocytic cell model","type":"article-journal","volume":"31"},"uris":["http://www.mendeley.com/documents/?uuid=a1a9105d-bb83-304f-8d0c-239e3dadf848"]},{"id":"ITEM-2","itemData":{"DOI":"10.1007/s12035-017-0667-3","ISBN":"1203501706","ISSN":"15591182","PMID":"28667487","abstract":"Obesity has been associated with increased chronic neuroinflammation and augmented risk of neurodegeneration. This is worsened during the normal aging process when the levels of endogenous gonadal hormones are reduced. In this study, we have assessed the protective actions of tibolone, a synthetic steroid with estrogenic actions, on T98G human astrocytic cells exposed to palmitic acid, a saturated fatty acid used to mimic obesity in vitro. Tibolone improved cell survival, and preserved mitochondrial membrane potential in palmitic acid-treated astrocytic cells. Although we did not find significant actions of tibolone on free radical production, it modulated astrocytic morphology after treatment with palmitic acid. These data suggest that tibolone protects astrocytic cells by preserving both mitochondrial functionality and morphological complexity.","author":[{"dropping-particle":"","family":"González-Giraldo","given":"Yeimy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Garcia-Segura","given":"Luis Miguel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Echeverria","given":"Valentina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barreto","given":"George E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Molecular Neurobiology","id":"ITEM-2","issue":"5","issued":{"date-parts":[["2017"]]},"page":"4453-4462","publisher":"Molecular Neurobiology","title":"Tibolone Preserves Mitochondrial Functionality and Cell Morphology in Astrocytic Cells Treated with Palmitic Acid","type":"article-journal","volume":"55"},"uris":["http://www.mendeley.com/documents/?uuid=f7219f5f-28d3-4b3e-9657-635307651a9f"]},{"id":"ITEM-3","itemData":{"DOI":"10.1007/s12035-018-1183-9","ISBN":"1203501811","ISSN":"15591182","PMID":"29916142","abstract":"Obesity is associated with an increase in the brain levels of saturated free fatty acids, such as palmitic acid (PA). Previous studies have shown that PA exerts proinflammatory actions and reduces cell viability in astrocyte cultures. In this study, we have assessed whether an alteration in autophagy is involved in the effects of PA on astrocytes. Primary astrocytes were obtained from the cerebral cortex of male and female CD1 mouse pups and were incubated for 4.5 or 24 h with 250–500 μM PA. PA increased the levels of LC3-II, an autophagosome marker, and reduced LC3-II flux in astrocytes, suggesting a blockade of autophagy. This effect was observed both after 4.5 and 24 h of treatment with PA. PA had additional effects after treatment for 24 h, increasing the expression of proinflammatory cytokines, decreasing cell viability, and increasing the levels of an endoplasmic reticulum stress marker. In addition, PA decreased the expression of estrogen receptors, but only in female astrocytes. However, the treatment with estradiol, estrogen receptor agonists, or inhibitor of estradiol synthesis did not counteract the action of PA on cell viability. Rapamycin, an autophagy inducer, was unable to prevent the effect of PA on cell viability. In addition, hydroxychloroquine, an autophagy blocker, did not cause per se astrocyte death. These findings suggest that the effect of PA on autophagy is not sufficient to induce astrocyte loss, which is only observed when prolonged PA treatment causes other alterations in astrocytes, such as increased inflammation and endoplasmic reticulum stress.","author":[{"dropping-particle":"","family":"Ortiz-Rodriguez","given":"Ana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Acaz-Fonseca","given":"Estefania","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Boya","given":"Patricia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arevalo","given":"Maria Angeles","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Garcia-Segura","given":"Luis M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Molecular Neurobiology","id":"ITEM-3","issue":"3","issued":{"date-parts":[["2018"]]},"page":"1665-1680","publisher":"Molecular Neurobiology","title":"Lipotoxic Effects of Palmitic Acid on Astrocytes Are Associated with Autophagy Impairment","type":"article-journal","volume":"56"},"uris":["http://www.mendeley.com/documents/?uuid=c71a1f9b-9537-4b8c-9ca9-ab426ef44f6b"]}],"mendeley":{"formattedCitation":"(González-Giraldo et al., 2017, 2019; Ortiz-Rodriguez et al., 2018)","plainTextFormattedCitation":"(González-Giraldo et al., 2017, 2019; Ortiz-Rodriguez et al., 2018)","previouslyFormattedCitation":"[18]–[20]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(González-Giraldo et al., 2017, 2019; Ortiz-Rodriguez et al., 2018), está la lipotoxicidad, la cual se relaciona con condiciones de amplia prevalencia como la obesidad ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/978-3-319-48382-5_8","ISSN":"22148019","PMID":"28585200","abstract":"Enlarged fat cells in obese adipose tissue diminish capacity to store fat and are resistant to the anti-lipolytic effect of insulin. Insulin resistance (IR)-associated S-nitrosylation of insulin-signaling proteins increases in obesity. In accordance with the inhibition of insulin-mediated anti-lipolytic action, plasma free fatty acid (FFA) levels increase. Additionally, endoplasmic reticulum stress stimuli induce lipolysis by activating cyclic adenosine monophosphate/Protein kinase A (cAMP/PKA) and extracellular signal-regulated kinase ½ (ERK1/2) signaling in adipocytes. Failure of packaging of excess lipid into lipid droplets causes chronic elevation of circulating fatty acids, which can reach to toxic levels within non-adipose tissues. Deleterious effects of lipid accumulation in non-adipose tissues are known as lipotoxicity. In fact, triglycerides may also serve a storage function for long-chain non-esterified fatty acids and their products such as ceramides and diacylglycerols (DAGs). Thus, excess DAG, ceramide and saturated fatty acids in obesity can induce chronic inflammation and have harmful effect on multiple organs and systems. In this context, chronic adipose tissue inflammation, mitochondrial dysfunction and IR have been discussed within the scope of lipotoxicity.","author":[{"dropping-particle":"","family":"Engin","given":"Ayse Basak","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Advances in Experimental Medicine and Biology","id":"ITEM-1","issued":{"date-parts":[["2017"]]},"page":"197-220","publisher":"Springer, Cham","title":"What is lipotoxicity?","type":"chapter","volume":"960"},"uris":["http://www.mendeley.com/documents/?uuid=a950c3f3-0d7e-3b5b-9628-da2bf274a71b"]}],"mendeley":{"formattedCitation":"(Engin, 2017)","plainTextFormattedCitation":"(Engin, 2017)","previouslyFormattedCitation":"[21]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Engin, 2017), y con la patogénesis de ND ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1194/jlr.M002329","ISSN":"0022-2275","abstract":"Abstract Childhood adrenoleukodystrophy (cALD) is a metabolic disorder in which very long-chain fatty acids (VLCFA) accumulate due to ALD protein gene defects, ultimately leading to lipotoxicity-induced neuroinflammatory demyelinating disease. Therefore, we examined VLCFA-mediated alterations in the metabolism of lipoxidative enzymes and inflammatory mediators in the cALD brain. 5-Lipoxygenase (5-LOX)-derived leukotrienes were significantly elevated in all the areas of white matter in the cALD brain. Unlike cyclooxygenase-2 expression, which was moderately high only in the plaque area, expression of 5-LOX and cytosolic phospholipase A2 was prominent in all the areas. This lipoxidative burden in the cALD brain was further shown by reduced levels of glutathione and enhanced expression of heat shock protein-70/manganese superoxide dismutase. These pathological observations were confirmed through in vitro mechanistic investigation. After increasing VLCFA through silencing Abcd1+Abcd2 in mouse primary astrocytes, enhanced expression of 5-LOX was observed, and this increased expression was blocked by treatment with monoenoic fatty acids. These results link the previously observed accumulation of VLCFA in cALD to the 5-LOX enzyme pathway. A similar increase in 5-LOX expression in astrocytes was also detected following treatment with exogenous VLCFA (C26:0). In sum, through 5-LOX activation, VLCFA accumulation causes a lipotoxic response consistent with cALD brain pathology. ","author":[{"dropping-particle":"","family":"Khan","given":"Mushfiquddin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Singh","given":"Jaspreet","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gilg","given":"Anne G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Uto","given":"Takuhiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Singh","given":"Inderjit","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Lipid Research","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2010","7"]]},"page":"1685-1695","publisher":"The American Society for Biochemistry and Molecular Biology","title":"Very long-chain fatty acid accumulation causes lipotoxic response via 5-lipoxygenase in cerebral adrenoleukodystrophy","type":"article-journal","volume":"51"},"uris":["http://www.mendeley.com/documents/?uuid=7e2f1939-0584-4f02-8851-fd64253185f8"]}],"mendeley":{"formattedCitation":"(Khan et al., 2010)","plainTextFormattedCitation":"(Khan et al., 2010)","previouslyFormattedCitation":"[22]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Khan et al., 2010). Por otro lado, el sncRNA astrocitario puede secretarse en Vesículas Extracelulares (EV), las cuales atraviesan la barrera hematoencefálica para localizarse en tejidos periféricos ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/S12964-021-00730-1","ISSN":"1478-811X","PMID":"33892745","abstract":"The use of exosomes in clinical settings is progressively becoming a reality, as clinical trials testing exosomes for diagnostic and therapeutic applications are generating remarkable interest from the scientific community and investors. Exosomes are small extracellular vesicles secreted by all cell types playing intercellular communication roles in health and disease by transferring cellular cargoes such as functional proteins, metabolites and nucleic acids to recipient cells. An in-depth understanding of exosome biology is therefore essential to ensure clinical development of exosome based investigational therapeutic products. Here we summarise the most up-to-date knowkedge about the complex biological journey of exosomes from biogenesis and secretion, transport and uptake to their intracellular signalling. We delineate the major pathways and molecular players that influence each step of exosome physiology, highlighting the routes of interest, which will be of benefit to exosome manipulation and engineering. We highlight the main controversies in the field of exosome research: their adequate definition, characterisation and biogenesis at plasma membrane. We also delineate the most common identified pitfalls affecting exosome research and development. Unravelling exosome physiology is key to their ultimate progression towards clinical applications.","author":[{"dropping-particle":"","family":"Gurung","given":"Sonam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Perocheau","given":"Dany","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Touramanidou","given":"Loukia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baruteau","given":"Julien","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Cell Communication and Signaling 2021 19:1","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2021","4","23"]]},"page":"1-19","publisher":"BioMed Central","title":"The exosome journey: from biogenesis to uptake and intracellular signalling","type":"article-journal","volume":"19"},"uris":["http://www.mendeley.com/documents/?uuid=715ae2e6-ee26-36da-a702-839c9bbf4593"]},{"id":"ITEM-2","itemData":{"DOI":"10.3390/IJMS221910553","ISSN":"1422-0067","PMID":"34638890","abstract":"Extracellular vesicles (EVs) are composed of lipid bilayer membranes and contain various molecules, such as mRNA and microRNA (miRNA), that regulate the functions of the recipient cell. Recent studies have reported the importance of EV-mediated intercellular communication in the brain. The brain contains several types of cells, including neurons and glial cells. Among them, astrocytes are the most abundant glial cells in the mammalian brain and play a wide range of roles, from structural maintenance of the brain to regulation of neurotransmission. Furthermore, since astrocytes can take up EVs, it is possible that EVs originating from inside and outside the brain affect astrocyte function, which in turn affects brain function. However, it has not been fully clarified whether the specific targeting mechanism of EVs to astrocytes as recipient cells exists. In recent years, EVs have attracted attention as a cell-targeted therapeutic approach in various organs, and elucidation of the targeting mechanism of EVs to astrocytes may pave the way for new therapies for brain diseases. In this review, we focus on EVs in the brain that affect astrocyte function and discuss the targeting mechanism of EVs to astrocytes.","author":[{"dropping-particle":"","family":"Ogaki","given":"Ari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ikegaya","given":"Yuji","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koyama","given":"Ryuta","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Molecular Sciences 2021, Vol. 22, Page 10553","id":"ITEM-2","issue":"19","issued":{"date-parts":[["2021","9","29"]]},"page":"10553","publisher":"Multidisciplinary Digital Publishing Institute","title":"Extracellular Vesicles Taken up by Astrocytes","type":"article-journal","volume":"22"},"uris":["http://www.mendeley.com/documents/?uuid=60aa06fc-206a-3476-ace6-35fbc436b718"]}],"mendeley":{"formattedCitation":"(Gurung et al., 2021; Ogaki et al., 2021)","plainTextFormattedCitation":"(Gurung et al., 2021; Ogaki et al., 2021)","previouslyFormattedCitation":"[23],[24]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Gurung et al., 2021; Ogaki et al., 2021), y expresan en su superficie proteínas de la célula que los originó que pueden ser célula-específicas. Así, biofluidos como la sangre, pueden emplearse en pruebas mucho menos invasivas y complejas que las usadas actualmente, para estudiar firmas de sncRNA astrocitarias, más precisas, que facilitarán la evaluación de ND en etapas más tempranas, que podrían iniciar hasta 30 años antes del diagnóstico actual. Este avance, no obstante, requiere evaluar diferentes formas de separar las EV para estudiar su sncRNA, pues no existe ningún método de aislamiento estándar ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1080/20013078.2018.1535750","ISSN":"20013078","abstract":"The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.","author":[{"dropping-particle":"","family":"Théry","given":"Clotilde","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Witwer","given":"Kenneth W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aikawa","given":"Elena","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alcaraz","given":"Maria Jose","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Anderson","given":"Johnathon D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Andriantsitohaina","given":"Ramaroson","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Antoniou","given":"Anna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arab","given":"Tanina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Archer","given":"Fabienne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Atkin-Smith","given":"Georgia K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ayre","given":"D. 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Tampoco se conoce cuál es el efecto de la lipotoxicidad en el transcriptoma del ARN corto no codificante (sncRNome) de EV derivadas de astrocito (ADEV) humanos, ni como las alteraciones debidas a la lipotoxicidad alteran la red regulatoria generada por el sncRNA. Teniendo en cuenta que el ácido palmítico es el ácido graso más abundante de la dieta y del organismo, y se desregula en ND ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3389/fnins.2019.01410","ISSN":"1662453X","abstract":"Inflammation is a complex biological response to injuries, metabolic disorders or infections. In the brain, astrocytes play an important role in the inflammatory processes during neurodegenerative diseases. Recent studies have shown that the increase of free saturated fatty acids such as palmitic acid produces a metabolic inflammatory response in astrocytes generally associated with damaging mechanisms such as oxidative stress, endoplasmic reticulum stress, and autophagic defects. In this aspect, the synthetic neurosteroid tibolone has shown to exert protective functions against inflammation in neuronal experimental models without the tumorigenic effects exerted by sexual hormones such as estradiol and progesterone. However, there is little information regarding the specific mechanisms of tibolone in astrocytes during inflammatory insults. In the present study, we performed a genome-scale metabolic reconstruction of astrocytes that was used to study astrocytic response during an inflammatory insult by palmitate through Flux Balance Analysis methods and data mining. In this aspect, we assessed the metabolic fluxes of human astrocytes under three different scenarios: healthy (normal conditions), induced inflammation by palmitate, and tibolone treatment under palmitate inflammation. Our results suggest that tibolone reduces the L-glutamate-mediated neurotoxicity in astrocytes through the modulation of several metabolic pathways involved in glutamate uptake. We also identified a set of reactions associated with the protective effects of tibolone, including the upregulation of taurine metabolism, gluconeogenesis, cPPAR and the modulation of calcium signaling pathways. In conclusion, the different scenarios studied in our model allowed us to identify several metabolic fluxes perturbed under an inflammatory response and the protective mechanisms exerted by tibolone.","author":[{"dropping-particle":"","family":"Osorio","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pinzón","given":"Andrés","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Martín-Jiménez","given":"Cynthia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barreto","given":"George E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"González","given":"Janneth","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Frontiers in Neuroscience","id":"ITEM-1","issue":"January","issued":{"date-parts":[["2020"]]},"page":"1-14","title":"Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach","type":"article-journal","volume":"13"},"uris":["http://www.mendeley.com/documents/?uuid=ca597921-97ab-42a7-ad21-323b0e70383f"]},{"id":"ITEM-2","itemData":{"DOI":"10.3389/fphys.2017.00902","ISBN":"1664-042X","ISSN":"1664042X","PMID":"29167646","abstract":"Palmitic acid (PA) has been for long time negatively depicted for its putative detrimental health effects, shadowing its multiple crucial physiological activities. PA is the most common saturated fatty acid accounting for 20-30% of total fatty acids in the human body and can be provided in the diet or synthesized endogenously via de novo lipogenesis (DNL). PA tissue content seems to be controlled around a well-defined concentration, and changes in its intake do not influence significantly its tissue concentration because the exogenous source is counterbalanced by PA endogenous biosynthesis. Particular physiopathological conditions and nutritional factors may strongly induce DNL, resulting in increased tissue content of PA and disrupted homeostatic control of its tissue concentration. The tight homeostatic control of PA tissue concentration is likely related to its fundamental physiological role to guarantee membrane physical properties but also to consent protein palmitoylation, palmitoylethanolamide (PEA) biosynthesis, and in the lung an efficient surfactant activity. In order to maintain membrane phospholipids (PL) balance may be crucial an optimal intake of PA in a certain ratio with unsaturated fatty acids, especially PUFAs of both n-6 and n-3 families. However, in presence of other factors such as positive energy balance, excessive intake of carbohydrates (in particular mono and disaccharides), and a sedentary lifestyle, the mechanisms to maintain a steady state of PA concentration may be disrupted leading to an over accumulation of tissue PA resulting in dyslipidemia, hyperglycemia, increased ectopic fat accumulation and increased inflammatory tone via toll-like receptor 4. It is therefore likely that the controversial data on the association of dietary PA with detrimental health effects, may be related to an excessive imbalance of dietary PA/PUFA ratio which, in certain physiopathological conditions, and in presence of an enhanced DNL, may further accelerate these deleterious effects.","author":[{"dropping-particle":"","family":"Carta","given":"Gianfranca","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Murru","given":"Elisabetta","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Banni","given":"Sebastiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Manca","given":"Claudia","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Frontiers in Physiology","id":"ITEM-2","issue":"NOV","issued":{"date-parts":[["2017"]]},"page":"1-14","title":"Palmitic acid: Physiological role, metabolism and nutritional implications","type":"article-journal","volume":"8"},"uris":["http://www.mendeley.com/documents/?uuid=ce607fc5-4f74-4713-ab99-462c689052c5"]}],"mendeley":{"formattedCitation":"(Carta et al., 2017; Osorio et al., 2020)","plainTextFormattedCitation":"(Carta et al., 2017; Osorio et al., 2020)","previouslyFormattedCitation":"[26],[27]"},"properties":{"noteIndex":0},"schema":"https://github.com/citation-style-language/schema/raw/master/csl-citation.json"}(Carta et al., 2017; Osorio et al., 2020), se generará un insulto lipotóxico con ácido palmítico en astrocitos humanos normales (NHA) para estudiar las alteraciones del sncRNA en ADEV, cuyo efecto en la red regulatoria se estudiará con apoyo del instituto ZMNH de Alemania. Se espera validar in vitro la separación de ADEV con apoyo metodológico del Laboratorio de Vesículas Extracelulares y Comunicación Celular del INMEGEN de México, encontrando sncRNA desregulados en lipotoxicidad que puedan relacionarse con curso y patogénesis de ND. Referencias ADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY Basler, G., Nikoloski, Z., Larhlimi, A., & Barabási, A. (2016). Control of Fluxes in Metabolic Networks Authors : Contact information : Running title : Keywords : 956–968. https://doi.org/10.1177/0193945917697223 Bélanger, M., Allaman, I., & Magistretti, P. J. (2011). Brain energy metabolism: Focus on Astrocyte-neuron metabolic cooperation. Cell Metabolism, 14(6), 724–738. https://doi.org/10.1016/j.cmet.2011.08.016 Booth, H. D. E., Hirst, W. D., & Wade-Martins, R. (2017). The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis. Trends in Neurosciences, 40(6), 358. https://doi.org/10.1016/J.TINS.2017.04.001 Carta, G., Murru, E., Banni, S., & Manca, C. 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| Estado | Finalizado |
|---|---|
| Fecha de inicio/Fecha fin | 25/02/23 → 23/11/24 |
Palabras clave
- Astrocitos
- Exosomas
- Lipotoxicidad
- Microarn
Estado del Proyecto
- Sin definir
Financiación de proyectos
- Interna
- Pontificia Universidad Javeriana
Huella digital
Explore los temas de investigación que se abordan en este proyecto. Estas etiquetas se generan con base en las adjudicaciones/concesiones subyacentes. Juntos, forma una huella digital única.