Dual action of memantine in Alzheimer disease: a hypothesis
Tzong-Yuan Wu1, Chih-Ping Chen
1Department of Bioscience Technology, Chung Yuan Christian University, Chungli, Taiwan. tywu@cycu.edu.tw
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.
Conclusion:
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.
Insights
Memantine may treat Alzheimer disease (AD) by blocking N-methyl-D-aspartate receptors and inhibiting the expression of amyloid precursor protein and tau. This dual action offers a novel therapeutic strategy for AD.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Alzheimer disease (AD) is characterized by neuritic plaques and neurofibrillary tangles.
- Amyloid-beta peptide and tau protein are key components of these pathological hallmarks.
- Targeting the expression of these proteins is a promising therapeutic avenue for AD.
Purpose of the Study:
- To investigate the mechanisms of memantine in treating Alzheimer disease (AD).
- To hypothesize how memantine may reduce amyloid precursor protein (APP) and tau protein expression.
- To explore memantine's potential as an N-methyl-D-aspartate (NMDA) receptor antagonist and protein expression inhibitor.
Main Methods:
- Investigated memantine's effect on internal ribosome entry site (IRES)-mediated translation initiation.
- Utilized COS-1 cells to study the molecular mechanisms of memantine action.
Main Results:
- Memantine was found to inhibit IRES-mediated translation initiation in COS-1 cells.
- This inhibition suggests memantine can block the expression of amyloid precursor protein (APP) and tau.
- Memantine may reduce neuronal excitotoxicity via NMDA receptor antagonism.
Conclusions:
- Memantine exhibits a dual mechanism of action in Alzheimer disease (AD).
- It acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, reducing excitotoxicity.
- It also inhibits internal ribosome entry site (IRES)-mediated translation, decreasing APP and tau expression to ameliorate AD symptoms.
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