P2X7R 在神经炎症中的作用及其在阿尔茨海默病中的意义。

The role of P2X7R in neuroinflammation and implications in Alzheimer's disease.

机构信息

Department of Neurology, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Life Sci. 2021 Apr 15;271:119187. doi: 10.1016/j.lfs.2021.119187. Epub 2021 Feb 10.

DOI:10.1016/j.lfs.2021.119187

PMID:33577858

Abstract

Alzheimer's disease (AD) is the most common cause of dementia and is set to rise in prevalence as the global trends in population aging. The extracellular deposition of amyloid protein (Aβ) and the intracellular formation of neurofibrillary tangles in the brain have been recognized as the two core pathologies of AD. Over the past decades, the presence of neuroinflammation in the brain has been documented as the third core pathology of AD. In recent years, emerging evidence demonstrated that the purinergic receptor P2X7 (P2X7R) serves a critical role in microglia responses and neuroinflammation. Besides, targeting P2X7R by genetic or pharmacological strategies attenuates the symptoms and pathological changes of AD models, and P2X7R has been recognized as a promising therapeutic target for AD. In this review, we summarized the recent evidence concerning the roles of P2X7R in neuroinflammation and implications in AD pathogenesis.

摘要

阿尔茨海默病（AD）是痴呆症最常见的病因，随着全球人口老龄化趋势的发展，其发病率也将上升。大脑中细胞外淀粉样蛋白（Aβ）的沉积和细胞内神经原纤维缠结的形成已被认为是 AD 的两个核心病理学特征。在过去的几十年中，人们已经认识到大脑中的神经炎症是 AD 的第三个核心病理学特征。近年来，新出现的证据表明嘌呤能受体 P2X7（P2X7R）在小胶质细胞反应和神经炎症中起着关键作用。此外，通过遗传或药理学策略靶向 P2X7R 可以减轻 AD 模型的症状和病理变化，并且 P2X7R 已被认为是 AD 的有前途的治疗靶标。在这篇综述中，我们总结了 P2X7R 在神经炎症中的作用及其在 AD 发病机制中的意义的最新证据。