Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou 510006, China.
Laboratory of Regenerative Medicine in Sports Science, School of Physical Education and Sports Science, South China Normal University, Guangzhou 510006, China.
Aging Dis. 2024 Aug 1;15(4):1537-1564. doi: 10.14336/AD.2023.0907.
Alzheimer's disease, one of the most common forms of dementia, is characterized by a slow progression of cognitive impairment and neuronal loss. Currently, approved treatments for AD are hindered by various side effects and limited efficacy. Despite considerable research, practical treatments for AD have not been developed. Increasing evidence shows that glial cells, especially microglia and astrocytes, are essential in the initiation and progression of AD. During AD progression, activated resident microglia increases the ability of resting astrocytes to transform into reactive astrocytes, promoting neurodegeneration. Extensive clinical and molecular studies show the involvement of microglia and astrocyte-mediated neuroinflammation in AD pathology, indicating that microglia and astrocytes may be potential therapeutic targets for AD. This review will summarize the significant and recent advances of microglia and astrocytes in the pathogenesis of AD in three parts. First, we will review the typical pathological changes of AD and discuss microglia and astrocytes in terms of function and phenotypic changes. Second, we will describe microglia and astrocytes' physiological and pathological role in AD. These roles include the inflammatory response, "eat me" and "don't eat me" signals, Aβ seeding, propagation, clearance, synapse loss, synaptic pruning, remyelination, and demyelination. Last, we will review the pharmacological and non-pharmacological therapies targeting microglia and astrocytes in AD. We conclude that microglia and astrocytes are essential in the initiation and development of AD. Therefore, understanding the new role of microglia and astrocytes in AD progression is critical for future AD studies and clinical trials. Moreover, pharmacological, and non-pharmacological therapies targeting microglia and astrocytes, with specific studies investigating microglia and astrocyte-mediated neuronal damage and repair, may be a promising research direction for future studies regarding AD treatment and prevention.
阿尔茨海默病是最常见的痴呆症类型之一，其特征是认知障碍和神经元丧失的缓慢进展。目前，AD 的批准治疗方法受到各种副作用和疗效有限的限制。尽管进行了大量研究，但尚未开发出针对 AD 的实用治疗方法。越来越多的证据表明，神经胶质细胞，特别是小胶质细胞和星形胶质细胞，在 AD 的发生和进展中起着至关重要的作用。在 AD 进展过程中，激活的常驻小胶质细胞增加了静止星形胶质细胞转化为反应性星形胶质细胞的能力，从而促进神经退行性变。广泛的临床和分子研究表明，小胶质细胞和星形胶质细胞介导的神经炎症参与了 AD 病理学，表明小胶质细胞和星形胶质细胞可能是 AD 的潜在治疗靶点。本综述将从三个方面总结小胶质细胞和星形胶质细胞在 AD 发病机制中的重要而最新进展。首先，我们将回顾 AD 的典型病理变化，并讨论小胶质细胞和星形胶质细胞在功能和表型变化方面的作用。其次，我们将描述小胶质细胞和星形胶质细胞在 AD 中的生理和病理作用。这些作用包括炎症反应、“吃我”和“不吃我”信号、Aβ 播散、清除、突触丢失、突触修剪、髓鞘形成和脱髓鞘。最后，我们将回顾针对 AD 中小胶质细胞和星形胶质细胞的药理学和非药理学治疗方法。我们的结论是，小胶质细胞和星形胶质细胞在 AD 的启动和发展中至关重要。因此，了解小胶质细胞和星形胶质细胞在 AD 进展中的新作用，对于未来的 AD 研究和临床试验至关重要。此外，针对小胶质细胞和星形胶质细胞的药理学和非药理学治疗方法，以及针对小胶质细胞和星形胶质细胞介导的神经元损伤和修复的具体研究，可能是未来 AD 治疗和预防研究的一个有前途的研究方向。
