Castillo_2016_Neurotoxicol_57_291

Biochemically, Alzheimers disease (AD) is characterized by the presence of abnormal deposition of beta amyloid peptide (Abeta(1-42)), which is generated by proteolytic processing from its precursor, the amyloid precursor protein (APP) in a non-physiological pathway. The presence of Abeta(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 Alzheimers 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 Abeta(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 Abeta(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 Abeta(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.