title: Galanthamine decreases genotoxicity and cell death induced by β-amyloid peptide in SH-SY5Y cell line.
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.
authors: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo - USP, Brazil. Electronic address: wocastillo@usp.br.
authors: Willian O
authors: WO
authors: Castillo
authors: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo - USP, Brazil.
authors: Andrés F
authors: AF
authors: Aristizabal-Pachon
authors: Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo - USP, Brazil.
authors: Ana P
authors: AP
authors: de Lima Montaldi
authors: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo - USP, Brazil; Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo - USP, Brazil.
authors: Elza T
authors: ET
authors: Sakamoto-Hojo
authors: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo - USP, Brazil; Department of Biology, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo - USP, Brazil.
authors: Catarina S
authors: CS
authors: Takahashi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D020552:Comet Assay; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005702:Galantamine / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D016207:Cytokines; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D005702:Galantamine
keywords: Alzheimer disease; Comet assay; Micronucleus test