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P1–079: Beta‐amyloid–induced neurotoxicity might be reduced through AMPK‐mediated by donepezil
Author(s) -
Park Moon Ho,
Park KunWoo,
Kim Hyeon Soo
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.300
Subject(s) - donepezil , memantine , ampk , neurotoxicity , neuroprotection , pharmacology , chemistry , acetylcholinesterase , calcium in biology , protein kinase a , nmda receptor , intracellular , kinase , medicine , receptor , biochemistry , dementia , toxicity , enzyme , disease , organic chemistry
Background: Acetylcholinesterase inhibitors (AchEIs) and NMDA receptor anatagonist memantine are used for the treatment of Alzheimer’s disease. Recently, the AchEI donepezil and memantine were found to have neuroprotective effects. However, these protective mechanisms have not yet been clearly identified. AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis and a central player in glucose and lipid metabolism, is potentially implicated in the pathogensis of Alzheimer’s disease. We investigated the neuroprotective effects of donepezil and memantine against amyloid-b 1-42 (Ab42)-induced neurotoxicity and AMPK signal pathway in HN33 hippocampal cell line.Methods: The neuroprotective effects of treatment with donepezil andmemantine on Ab42-induced cell death, was measured by MTT assay. Expression levels of phosphorylation status of AMPK were analyzed by Western blot. Intracellular calcium concentration was measured with calcium indicator dye, fluo-3AM. Results:We reported that only donepezil increased intracellular calcium concentration and donepezil activated AMPK in HN33 cells with Ab42. Moreover, inhibition of AMPK resulted in blockage of donepezil-induced calcium uptake. Conclusions: These results suggest that donepezil might prevent Ab42-induced neurotoxicity through AMPK pathway.