Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95123 Catania, Italy.
Cells. 2022 Sep 1;11(17):2728. doi: 10.3390/cells11172728.
Alzheimer's disease (AD) is the most common form of dementia worldwide, with a complex, poorly understood pathogenesis. Cerebral atrophy, amyloid-β (Aβ) plaques, and neurofibrillary tangles represent the main pathological hallmarks of the AD brain. Recently, neuroinflammation has been recognized as a prominent feature of the AD brain and substantial evidence suggests that the inflammatory response modulates disease progression. Additionally, dysregulation of calcium (Ca) homeostasis represents another early factor involved in the AD pathogenesis, as intracellular Ca concentration is essential to ensure proper cellular and neuronal functions. Although growing evidence supports the involvement of Ca in the mechanisms of neurodegeneration-related inflammatory processes, scant data are available on its contribution in microglia and astrocytes functioning, both in health and throughout the AD continuum. Nevertheless, AD-related aberrant Ca signalling in astrocytes and microglia is crucially involved in the mechanisms underpinning neuroinflammatory processes that, in turn, impact neuronal Ca homeostasis and brain function. In this light, we attempted to provide an overview of the current understanding of the interactions between the glia cells-mediated inflammatory responses and the molecular mechanisms involved in Ca homeostasis dysregulation in AD.
阿尔茨海默病（AD）是全球最常见的痴呆症形式，其发病机制复杂且尚未被充分理解。脑萎缩、β淀粉样蛋白（Aβ）斑块和神经原纤维缠结是 AD 大脑的主要病理标志物。最近，神经炎症已被认为是 AD 大脑的一个显著特征，大量证据表明炎症反应调节疾病进展。此外，钙（Ca）稳态失调是 AD 发病机制中另一个早期因素，因为细胞内 Ca 浓度对于确保适当的细胞和神经元功能至关重要。尽管越来越多的证据支持 Ca 参与与神经退行性相关炎症过程的机制，但关于其在健康和 AD 连续体中星形胶质细胞和小胶质细胞功能中的作用的数据很少。然而，AD 相关的星形胶质细胞和小胶质细胞中异常的 Ca 信号在神经炎症过程的机制中起着至关重要的作用，而这些过程反过来又影响神经元 Ca 稳态和大脑功能。有鉴于此，我们试图概述当前对胶质细胞介导的炎症反应与 AD 中 Ca 稳态失调相关的分子机制之间相互作用的理解。
