Galanthamine decreases genotoxicity and cell death induced by β-amyloid peptide in SH-SY5Y cell line

TLDR: It is demonstrated that in addition to inhibition of acetylcholinesterase (AChE), galanthamine exerts antigenotoxic properties which may improve the development of new diseases-modifying agents.

Abstract: 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