Dual action of memantine in Alzheimer disease: a hypothesis.
OBJECTIVE
In 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.


RESULTS
Two neuropathologic characteristics of AD are neuritic plaques and neurofibrillary tangles. The major molecular components of the plaques and tangles are amyloid-beta peptide and tau, respectively. Drugs able to reduce the expression of amyloid-beta 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.


CONCLUSIONS
Memantine 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.
Wu
Tzong-Yuan
TY
Department of Bioscience Technology, Chung Yuan Christian University, Chungli, Taiwan. tywu@cycu.edu.tw
Chen
Chih-Ping
CP
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015259:Dopamine Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008559:Memantine / Q000737:chemistry / Q000494:pharmacology*; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012270:Ribosomes / Q000187:drug effects*; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D015259:Dopamine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016875:tau Proteins; D008559:Memantine