Wu Tzong-Yuan, Chen Chih-Ping
Department of Bioscience Technology, Chung Yuan Christian University, Chungli, Taiwan.
Taiwan J Obstet Gynecol. 2009 Sep;48(3):273-7. doi: 10.1016/S1028-4559(09)60303-X.
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.
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.
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.
在本研究中，我们提出一个假设来解释美金刚治疗阿尔茨海默病（AD）的作用机制。美金刚可能会降低淀粉样前体蛋白和tau蛋白的表达，并且在大脑中作为N-甲基-D-天冬氨酸受体的拮抗剂发挥作用。
AD的两个神经病理学特征是神经炎性斑块和神经原纤维缠结。斑块和缠结的主要分子成分分别是β-淀粉样肽和tau。能够降低β-淀粉样蛋白和tau蛋白表达的药物为AD提供了潜在的药物治疗方法。我们发现美金刚在COS-1细胞中抑制内部核糖体进入位点介导的翻译起始。这表明美金刚不仅可能抑制神经元兴奋性毒性，还可能作为内部核糖体进入位点的抑制剂，来阻断神经元中淀粉样前体蛋白和tau的表达。
美金刚可能不仅作为N-甲基-D-天冬氨酸受体的拮抗剂发挥作用，还作为内部核糖体进入位点的抑制剂来阻断淀粉样前体蛋白和tau的表达，从而改善AD的症状。
