TY - JOUR
T1 - Galanthamine decreases genotoxicity and cell death induced by β-amyloid peptide in SH-SY5Y cell line
AU - Castillo, Willian O.
AU - Aristizabal-Pachon, Andrés F.
AU - de Lima Montaldi, Ana P.
AU - Sakamoto-Hojo, Elza T.
AU - Takahashi, Catarina S.
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Biochemically, Alzheimeŕs disease (AD) is characterized by the presence of abnormal deposition of beta amyloid peptide (Aβ(1-42)), which is generated by proteolytic processing from its precursor, the amyloid precursor protein (APP) in a non-physiological pathway. The presence of Aβ(1-42) in the brain is strongly correlated with cognitive impairment, cholinergic deficiency, bioenergetics disruption, cell death and DNA damage. Galanthamine is an acetylcholinesterase inhibitor (AChEI) used to symptomatic treatment of Alzheimeŕs disease (AD). Several studies have showed that galanthamine has antioxidant properties, anti-apoptotic action and also promotes neurogenesis; however, it is unknown whether galanthamine may present protection mechanisms against Aβ(1-42)-induced genomic instability. To understand the mechanisms of this neuroprotection, we studied the effects of galanthamine on the cell toxicity and DNA strand breaks induced by Aβ(1-42) using a set of biomarkers such as clonogenic assay, cytokinesis block micronucleus cytome (CBNM-cyt) and comet assay. The results showed that galanthamine treatments were capable to significantly reduce the Aβ(1-42)-induced cytotoxicity and genotoxicity. In conclusion, this study demonstrated that in addition to inhibition of acetylcholinesterase (AChE), galanthamine exerts antigenotoxic properties. This relevant property of galanthamine is worthwhile exploring further which may improve the development of new diseases-modifying agents.
AB - Biochemically, Alzheimeŕs disease (AD) is characterized by the presence of abnormal deposition of beta amyloid peptide (Aβ(1-42)), which is generated by proteolytic processing from its precursor, the amyloid precursor protein (APP) in a non-physiological pathway. The presence of Aβ(1-42) in the brain is strongly correlated with cognitive impairment, cholinergic deficiency, bioenergetics disruption, cell death and DNA damage. Galanthamine is an acetylcholinesterase inhibitor (AChEI) used to symptomatic treatment of Alzheimeŕs disease (AD). Several studies have showed that galanthamine has antioxidant properties, anti-apoptotic action and also promotes neurogenesis; however, it is unknown whether galanthamine may present protection mechanisms against Aβ(1-42)-induced genomic instability. To understand the mechanisms of this neuroprotection, we studied the effects of galanthamine on the cell toxicity and DNA strand breaks induced by Aβ(1-42) using a set of biomarkers such as clonogenic assay, cytokinesis block micronucleus cytome (CBNM-cyt) and comet assay. The results showed that galanthamine treatments were capable to significantly reduce the Aβ(1-42)-induced cytotoxicity and genotoxicity. In conclusion, this study demonstrated that in addition to inhibition of acetylcholinesterase (AChE), galanthamine exerts antigenotoxic properties. This relevant property of galanthamine is worthwhile exploring further which may improve the development of new diseases-modifying agents.
KW - Alzheimer disease
KW - Comet assay
KW - Micronucleus test
UR - http://www.scopus.com/inward/record.url?scp=84992695414&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2016.10.013
DO - 10.1016/j.neuro.2016.10.013
M3 - Article
C2 - 27793617
AN - SCOPUS:84992695414
SN - 0161-813X
VL - 57
SP - 291
EP - 297
JO - NeuroToxicology
JF - NeuroToxicology
ER -