Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Daping, Chongqing 400042, China.
Biochem Pharmacol. 2011 Nov 15;82(10):1500-9. doi: 10.1016/j.bcp.2011.06.040. Epub 2011 Jul 5.
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.
阿尔茨海默病（AD）是最常见的痴呆症形式，其特征是淀粉样斑块沉积、神经元纤维缠结积聚、神经元突起退化、神经元丧失以及认知功能的进行性丧失。AD 的发病机制尚未完全阐明，目前尚无有效的疾病修饰治疗方法。最近的研究表明，泛神经生长因子受体 p75NTR 是 AD 发病机制中的一个关键因素。在这篇综述中，我们讨论了 p75NTR 在 AD 中淀粉样β（Aβ）产生、神经元死亡、神经元突起退化、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 标志物的不同方面以及打破促进 AD 发病机制级联反应的 p75NTR 介导的正反馈环的各种治疗策略的观点。
