Dual Action of Memantine in Alzheimer Disease: A Hypothesis

SummaryObjectiveIn this study, we proposed a hypothesis to explain the mechanisms of memantine action in treating Alzheimer disease (AD). Memantine may reduce the expression of amyloid precursor protein and tau protein, as well as acting as an antagonist of N-methyl-d-aspartate receptors in the brain.ResultsTwo neuropathologic characteristics of AD are neuritic plaques and neurofibrillary tangles. The major molecular components of the plaques and tangles are amyloid-β peptide and tau, respectively. Drugs able to reduce the expression of amyloid-β and tau protein provide potential pharmaceutical treatments for AD. We found that memantine inhibited internal ribosome entry site-mediated translation initiation in COS-1 cells. This suggests that the memantine may not only inhibit neuronal excitotoxicity, but also act as an inhibitor of the internal ribosome entry site, to block the expression of amyloid precursor protein and tau in neurons.ConclusionMemantine may function not only as an antagonist of N-methyl-D-aspartate receptors, but also as an inhibitor of the internal ribosome entry site to block the expression of amyloid precursor protein and tau, and so ameliorate the symptoms of AD.