TY - JOUR
T1 - Epigenetic regulation exerted by Caliphruria subedentata and galantamine
T2 - an in vitro and in silico approach for mimic Alzheimer’s disease
AU - Castillo Ordoñez, Willian Orlando
AU - Aristizabal-Pachon, Andrés F.
AU - Alves, Levy Bueno
AU - Giuliatti, Silvana
N1 - Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2024
Y1 - 2024
N2 - At the interface between genes and environment, epigenetic mechanisms, including DNA methylation and histone modification, regulate neurogenic processes such as differentiation, proliferation, and maturation of neural stem cells. However, these mechanisms are altered in Alzheimer’s disease (AD), a neurodegenerative condition that mainly affects older adults. Since epigenetic mechanisms are known to be reversible, a number of molecules from natural sources are being studied as epigenetic regulators in AD. Recently, in vitro and in silico studies have shown that C. subedentata and its alkaloids modulated neurotoxicity. However, studies exploring the epigenetic activity of these alkaloids are limited. We conducted a set of bioassays to evaluate neuronal differentiation and the sensitivity of undifferentiated SH-SY5 cells against a neurotoxic stimulus. In addition, we analyzed the methylation profiles in genes such as APP, PSI, and BACE1 due to their role in amyloid processing. Docking and molecular dynamic analysis were used to explore the effect exerted by C. subedentata alkaloids on the regulation of histone deacetylases (HDAC2, HDAC3 and HDAC7). The results demonstrated that C. subedentata and galantamine induce neuronal differentiation and protect the undifferentiated SH-SY5Y cells against Aβ(1-42)-induced neurotoxicity. The methylation profiles of the studied genes show no statistically significant differences between C. subedentata, galantamine. However, these findings should be interpreted with caution, since small changes in methylation promoters in the brain could not be easily detected. Results from in silico approaches describe for the first time the potential promissing epigenetic effects of galantamine by regulating HDAC3 and HDAC7 modification. Communicated by Ramaswamy H. Sarma.
AB - At the interface between genes and environment, epigenetic mechanisms, including DNA methylation and histone modification, regulate neurogenic processes such as differentiation, proliferation, and maturation of neural stem cells. However, these mechanisms are altered in Alzheimer’s disease (AD), a neurodegenerative condition that mainly affects older adults. Since epigenetic mechanisms are known to be reversible, a number of molecules from natural sources are being studied as epigenetic regulators in AD. Recently, in vitro and in silico studies have shown that C. subedentata and its alkaloids modulated neurotoxicity. However, studies exploring the epigenetic activity of these alkaloids are limited. We conducted a set of bioassays to evaluate neuronal differentiation and the sensitivity of undifferentiated SH-SY5 cells against a neurotoxic stimulus. In addition, we analyzed the methylation profiles in genes such as APP, PSI, and BACE1 due to their role in amyloid processing. Docking and molecular dynamic analysis were used to explore the effect exerted by C. subedentata alkaloids on the regulation of histone deacetylases (HDAC2, HDAC3 and HDAC7). The results demonstrated that C. subedentata and galantamine induce neuronal differentiation and protect the undifferentiated SH-SY5Y cells against Aβ(1-42)-induced neurotoxicity. The methylation profiles of the studied genes show no statistically significant differences between C. subedentata, galantamine. However, these findings should be interpreted with caution, since small changes in methylation promoters in the brain could not be easily detected. Results from in silico approaches describe for the first time the potential promissing epigenetic effects of galantamine by regulating HDAC3 and HDAC7 modification. Communicated by Ramaswamy H. Sarma.
KW - Docking
KW - Molecular
KW - Neurogenesis
KW - methylation analysis
KW - neurotoxicity
UR - http://www.scopus.com/inward/record.url?scp=85173773066&partnerID=8YFLogxK
U2 - 10.1080/07391102.2023.2261034
DO - 10.1080/07391102.2023.2261034
M3 - Article
C2 - 37814967
AN - SCOPUS:85173773066
SN - 0739-1102
VL - 42
SP - 11215
EP - 11230
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 20
ER -