Roles of p75NTR in the pathogenesis of Alzheimer's disease: a novel therapeutic target.
Roles of p75NTR in the pathogenesis of Alzheimer's disease: a novel therapeutic target.
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DOI：
10.1016/j.bcp.2011.06.040
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发表时间：
2011-11
影响因子：
5.8
通讯作者：
Fan Zeng;Jian-Jun Lu;Xin-Fu Zhou;Yanjiang Wang
中科院分区：
文献类型：
--
作者：
Fan Zeng;Jian-Jun Lu;Xin-Fu Zhou;Yanjiang Wang
阿尔茨海默病（AD）是最常见的痴呆形式，其特征是淀粉样斑块沉积、神经元纤维缠结积聚、神经突变性、神经元丧失和认知功能的进行性丧失。阿尔茨海默病的发病机制尚不完全清楚，目前也没有有效的疾病改善疗法。最近的研究表明，泛神经营养因子受体p75NTR是参与AD发病的关键因素。在这篇综述中，我们讨论了p75NTR在AD中淀粉样蛋白β (a β)的产生、神经元死亡、神经突变性、tau过度磷酸化、细胞周期再进入和认知能力下降中的作用，并提出p75NTR是开发AD治疗药物的潜在靶点。最后，我们提供了针对与p75NTR功能相关的AD标志的不同方面开发各种治疗策略的观点，并打破了p75NTR介导的促进AD发病机制级联反应的正反馈回路。
Alzheimer's disease (AD), the most common form of dementia, is characterized by the deposition of amyloid plaques, accumulation of fibrillary tangles in neurons, neurite degeneration, loss of neurons, and a progressive loss of cognitive function. The pathogenesis of AD is not fully understood, and no strong disease-modifying therapies are currently available. Recent studies suggest that the pan-neurotrophin receptor, p75NTR, is a critical factor involved in the pathogenesis of AD. In this review, we have discussed the roles of p75NTR in the production of amyloid-beta (Aβ), neuronal death, neurite degeneration, tau hyperphosphorylation, cell cycle re-entry and cognition decline in AD, and proposed that p75NTR is a potential target for the development of therapeutic drugs for AD. Finally we provide perspectives in developing various therapeutic strategies targeting different aspects of AD hallmarks which relate to p75NTR functions and breaking the p75NTR-mediated positive feedback loop which promotes the cascades in the pathogenesis of AD.