Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
J Biol Chem. 2024 May;300(5):107306. doi: 10.1016/j.jbc.2024.107306. Epub 2024 Apr 20.
Alzheimer's disease (AD) is the most common form of dementia defined by two key pathological characteristics in the brain, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Microglia, the primary innate immune cells of the central nervous system (CNS), provide neuroprotection through Aβ and tau clearance but may also be neurotoxic by promoting neuroinflammation to exacerbate Aβ and tau pathogenesis in AD. Recent studies have demonstrated the importance of microglial utilization of nutrients and trace metals in controlling their activation and effector functions. Trace metals, such as zinc, have essential roles in brain health and immunity, and zinc dyshomeostasis has been implicated in AD pathogenesis. As a result of these advances, the mechanisms by which zinc homeostasis influences microglial-mediated neuroinflammation in AD is a topic of continuing interest since new strategies to treat AD are needed. Here, we review the roles of zinc in AD, including zinc activation of microglia, the associated neuroinflammatory response, and the application of these findings in new therapeutic strategies.
阿尔茨海默病（AD）是最常见的痴呆症形式，其特征是大脑中有两个关键的病理特征，即淀粉样β（Aβ）斑块和由过度磷酸化的 tau 组成的神经原纤维缠结（NFTs）。小胶质细胞是中枢神经系统（CNS）的主要固有免疫细胞，通过清除 Aβ和 tau 提供神经保护作用，但也可能通过促进神经炎症来加剧 AD 中的 Aβ和 tau 发病机制而具有神经毒性。最近的研究表明，小胶质细胞利用营养物质和痕量金属来控制其激活和效应功能的重要性。痕量金属，如锌，在大脑健康和免疫中起着重要作用，AD 发病机制中涉及锌动态平衡失调。由于这些进展，锌稳态如何影响 AD 中小胶质细胞介导的神经炎症的机制是一个持续关注的话题，因为需要新的 AD 治疗策略。在这里，我们综述了锌在 AD 中的作用，包括锌对小胶质细胞的激活、相关的神经炎症反应，以及这些发现在新的治疗策略中的应用。
