Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang Province, China.
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
J Alzheimers Dis. 2023;94(s1):S335-S354. doi: 10.3233/JAD-221064.
The neurovascular unit (NVU) is involved in the pathological changes in Alzheimer's disease (AD). The NVU is a structural and functional complex that maintains microenvironmental homeostasis and metabolic balance in the central nervous system. As one of the most important components of the NVU, microglia not only induce blood-brain barrier breakdown by promoting neuroinflammation, the infiltration of peripheral white blood cells and oxidative stress but also mediate neurovascular uncoupling by inducing mitochondrial dysfunction in neurons, abnormal contraction of cerebral vessels, and pericyte loss in AD. In addition, microglia-mediated dysfunction of cellular components in the NVU, such as astrocytes and pericytes, can destroy the integrity of the NVU and lead to NVU impairment. Therefore, we review the mechanisms of microglia-mediated NVU dysfunction in AD. Furthermore, existing therapeutic advancements aimed at restoring the function of microglia and the NVU in AD are discussed. Finally, we predict the role of pericytes in microglia-mediated NVU dysfunction in AD is the hotspot in the future.
神经血管单位 (NVU) 参与阿尔茨海默病 (AD) 的病理变化。NVU 是一个结构和功能复杂的单位,可维持中枢神经系统的微环境稳态和代谢平衡。作为 NVU 的最重要组成部分之一,小胶质细胞不仅通过促进神经炎症、外周白细胞浸润和氧化应激导致血脑屏障破裂,而且还通过诱导神经元线粒体功能障碍、脑血管异常收缩和 AD 中周细胞丢失来介导神经血管解偶联。此外,小胶质细胞介导的 NVU 中细胞成分(如星形胶质细胞和周细胞)的功能障碍会破坏 NVU 的完整性并导致 NVU 损伤。因此,我们综述了 AD 中小胶质细胞介导的 NVU 功能障碍的机制。此外,还讨论了针对 AD 中恢复小胶质细胞和 NVU 功能的现有治疗进展。最后,我们预测周细胞在 AD 中小胶质细胞介导的 NVU 功能障碍中的作用将是未来的热点。
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