Rapamycin, Autophagy, and Alzheimer's Disease.
Rapamycin, Autophagy, and Alzheimer's Disease.
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发表时间：
2013-06
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通讯作者：
Z. Cai;Liang-Jun Yan
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作者：
Z. Cai;Liang-Jun Yan
阿尔茨海默病（Alzheimer's disease，AD）是一种以认知功能障碍和多种病理损害为特征的神经退行性疾病。在分子水平上，AD的特征在于明显的淀粉样蛋白β（Aβ）产生和tau过度磷酸化。因此，可以减弱Aβ积聚和tau过度磷酸化的药理学药物具有治疗AD的潜在前景。雷帕霉素是哺乳动物雷帕霉素靶蛋白（mTOR）的抑制剂，被认为是这样的药理学试剂之一。它在神经退行性疾病中具有神经保护作用，其主要作用被认为是通过增强自噬，自噬是一种生物学过程，不仅有助于清除突变蛋白，而且还显著减少毒性蛋白质聚集体（如Aβ）的积聚。由于雷帕霉素增强自噬与AD病理过程的消除（例如Aβ和神经元缠结（NTFs）的清除以及tau过度磷酸化的减少和认知的改善）相关，因此雷帕霉素正在成为AD的潜在治疗化合物。
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and multiple pathological lesions. At the molecular level, AD is characterized by overt amyloid β (Aβ) production and tau hyper-phosphorylation. Hence, pharmacological agents that can attenuate Aβ accumulation and tau hyper-phosphorylation have potential promise for treatment of AD. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is believed to be one of such pharmacological agents. It is neuroprotective in neurodegenerative diseases and its primary action is thought to be via enhancement of autophagy, a biological process that not only facilitates the clearance of mutant proteins but also significantly reduces the build-up of toxic protein aggregates such as Aβ. Since rapamycin enhancement of autophagy has been associated with abrogation of AD pathological processes such as clearance of Aβ and neurofibrillary tangles (NTFs) as well as reduction of tau hyper-phosphorylation and improvement of cognition, rapamycin is emerging as a potential therapeutic compound for AD.