Alzheimer’s disease (AD) is a neurodegenerative disease that leads to progressive loss of memory and dementia. The pathological hallmarks of AD include extracellular accumulation of amyloid-β peptides forming senile plaques and intracellular accumulation of Tau oligomers and filamentous species. Tau is a microtubule-binding protein that stabilizes tubulin to form microtubules under physiological condition. In AD/ pathological condition, Tau detaches from microtubules and aggregates to form oligomers of different sizes and filamentous species such as paired helical filaments. Microglia are the resident brain macrophages that are involved in the phagocytosis of microbes, cellular debris, misfolded and aggregated proteins. Chemokine receptor, CX3CR1 is mostly expressed on microglia and is involved in maintaining the microglia in a quiescent state by binding to its ligand, fractalkine (CX3CL1), which is expressed in neurons as both soluble or membrane-bound state. Hence, under physiological conditions, the CX3CR1/CX3CL1 axis plays a significant role in maintaining the central nervous system (CNS) homeostasis. Further, CX3CR1/CX3CL1 signalling is involved in the synthesis of anti-inflammatory cytokines and also has a significant role in cytoskeletal rearrangement, migration, apoptosis and proliferation. In AD brain, the expression level of fractalkine is reduced, and hence Tau competes to interact with its receptor, CX3CR1. In microglia, phagocytosis and internalization of extracellular Tau species occurs in the presence of a chemokine receptor, CX3CR1 which binds directly to Tau and promotes its internalization. In this review, the pathophysiological roles of CX3CR1/fractalkine signalling in microglia and neurons at different stages of Alzheimer’s disease and the possible role of CX3CR1/Tau signalling has been widely discussed.

中文翻译：

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Tau 与趋化因子受体 CX3CR1 的相互作用及其对小胶质细胞激活、迁移和增殖的影响。


阿尔茨海默病（AD）是一种神经退行性疾病，会导致记忆力逐渐丧失和痴呆。 AD 的病理特征包括形成老年斑的淀粉样β肽的细胞外积累以及 Tau 寡聚物和丝状物质的细胞内积累。 Tau是一种微管结合蛋白，在生理条件下稳定微管蛋白形成微管。在AD/病理条件下，Tau蛋白从微管分离并聚集形成不同大小的寡聚体和丝状物种，例如成对的螺旋丝。小胶质细胞是大脑中常驻的巨噬细胞，参与微生物、细胞碎片、错误折叠和聚集蛋白质的吞噬作用。趋化因子受体 CX3CR1 主要在小胶质细胞上表达，并通过与其配体 fractalkine (CX3CL1) 结合参与维持小胶质细胞处于静止状态，该配体在神经元中以可溶或膜结合状态表达。因此，在生理条件下，CX3CR1/CX3CL1轴在维持中枢神经系统（CNS）稳态中发挥着重要作用。此外，CX3CR1/CX3CL1信号传导参与抗炎细胞因子的合成，并且在细胞骨架重排、迁移、凋亡和增殖中也具有重要作用。在 AD 大脑中，fractalkine 的表达水平降低，因此 Tau 与其受体 CX3CR1 竞争相互作用。在小胶质细胞中，细胞外 Tau 物质的吞噬作用和内化发生在趋化因子受体 CX3CR1 存在的情况下，CX3CR1 直接与 Tau 结合并促进其内化。 在这篇综述中，CX3CR1/fractalkine 信号在阿尔茨海默病不同阶段的小胶质细胞和神经元中的病理生理作用以及 CX3CR1/Tau 信号的可能作用得到了广泛讨论。