阿尔茨海默病中的突触功能障碍：机制与治疗策略。

Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies.

机构信息

Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, China.

Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, China.

出版信息

Pharmacol Ther. 2019 Mar;195:186-198. doi: 10.1016/j.pharmthera.2018.11.006. Epub 2018 Nov 12.

DOI:10.1016/j.pharmthera.2018.11.006

PMID:30439458

Abstract

Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly population, is characterized by progressive cognitive decline and pathological hallmarks of amyloid plaques and neurofibrillary tangles. However, its pathophysiological mechanisms are poorly understood, and diagnostic tools and interventions are limited. Here, we review recent research on the amyloid hypothesis and beta-amyloid-induced dysfunction of neuronal synapses through distinct cell surface receptors. We also review how tau protein leads to synaptotoxicity through pathological modification, localization, and propagation. Finally, we discuss experimental therapeutics for AD and propose potential applications of disease-modifying strategies targeting synaptic failure for improved treatment of AD.

摘要

阿尔茨海默病（AD）是老年人中最常见的神经退行性疾病，其特征是进行性认知能力下降和淀粉样斑块和神经原纤维缠结的病理标志。然而，其病理生理机制尚不清楚，诊断工具和干预措施也有限。在这里，我们回顾了最近关于淀粉样蛋白假说的研究，以及β-淀粉样蛋白通过不同的细胞表面受体引起神经元突触功能障碍。我们还回顾了tau 蛋白如何通过病理性修饰、定位和传播导致突触毒性。最后，我们讨论了 AD 的实验治疗方法，并提出了针对突触故障的疾病修饰策略的潜在应用，以改善 AD 的治疗。