Alzheimer‘s disease (AD) is a neurodegenerative disease mainly associated with aging, oxidative stress and genetic mutations. There are two pathological proteins involved in AD; Amyloid-β peptide and microtubule-associated protein Tau (MAPT). The β- and γ-secretase enzyme cleaves the Amyloid precursor protein, which results in the formation of extracellular plaques in brain. While, Tau undergoes hyperphosphorylation and other post-translational modifications (PTMs), which eventually generates Tau oligomers, and intracellular neurofibrillary tangles (NFTs) in neurons. Moreover, the brain-resident glia and infiltrated macrophages elevate the level of CNS inflammation, which trigger the oxidative damage of neuronal circuits by reactive oxygen species and NO. Microglia is the primary immune cell in the central nervous system (CNS), which is continuously surveilling the neuronal synapses and pathogen invasion. Microglia in the resting state is called ‘Ramified’, which possess long surveilling extensions with a small cell body. But, upon activation, microglia retracts the cellular extensions and transform into round migratory cells, called as ‘Amoeboid’ state. Activated microglia undergoes actin remodeling by forming lamellipodia and filopodia, which directs the migratory axis while podosomes formed are involved in extracellular matrix degradation for invasion. Protein-aggregates in malfunctioning synapses and in CNS milieu can be detected by microglia, which results in its activation and migration. Subsequently, the phagocytosis of synapses leads to the inflammatory burst and memory loss. The extracellular nucleotides released from damaged neurons and the cytokine-chemokine gradients allow the neighboring microglia and macrophages to migrate-infiltrate at the site of neuronal-damage. The ionotropic (P2XR) and metabotropic (P2YR) purinergic receptor recognize extracellular ATP/ADP, which propagates through the intracellular calcium signaling, chemotaxis, phagocytosis and inflammation. The P2Y receptors give ‘find me’ or ‘eat me’ signals to microglia to either migrate or phagocytose cellular debris. Further, the actin cytoskeleton helps microglia to mediate directed chemotaxis and neuronal repair during neurodegeneration. Hence, we aim to emphasize the connection between purinergic signaling and actin-driven mechanical movements of microglia for migration and inflammation in AD.

阿尔茨海默氏病（AD）是一种主要与衰老，氧化应激和基因突变有关的神经退行性疾病。AD中有两种病理蛋白：淀粉样β肽和微管相关蛋白Tau（MAPT）。β-和γ-分泌酶会裂解淀粉样蛋白前体蛋白，从而导致大脑中细胞外斑块的形成。同时，Tau发生过度磷酸化和其他翻译后修饰（PTM），最终在神经元中产生Tau寡聚物和细胞内神经原纤维缠结（NFT）。此外，大脑中的神经胶质细胞和浸润的巨噬细胞会升高中枢神经系统炎症的水平，从而触发神经元回路被活性氧和一氧化氮的氧化损伤。小胶质细胞是中枢神经系统（CNS）的主要免疫细胞，持续监测神经元突触和病原体入侵。处于静止状态的小胶质细胞被称为“ Ramified”，具有较长的监视范围和较小的细胞体。但是，激活后，小胶质细胞会收缩细胞延伸并转化为圆形迁移细胞，称为“变形虫”状态。活化的小胶质细胞通过形成lamellipodia和filopodia来进行肌动蛋白重塑，从而指导迁移轴，而形成的足小泡则参与细胞外基质的降解。小胶质细胞可以检测到功能异常的突触和中枢神经系统环境中的蛋白质聚集体，从而导致其活化和迁移。随后，突触的吞噬作用导致炎性爆发和记忆丧失。从受损神经元释放的细胞外核苷酸和细胞因子趋化因子梯度使邻近的小胶质细胞和巨噬细胞在神经元损伤部位迁移并浸润。离子型（P2XR）和代谢型（P2YR）嘌呤能受体识别细胞外ATP / ADP，其通过细胞内钙信号传导，趋化性，吞噬作用和炎症传播。P2Y受体向小胶质细胞发出“发现”或“吞噬”信号，以迁移或吞噬细胞碎片。此外，肌动蛋白的细胞骨架有助于小胶质细胞在神经变性期间介导定向趋化性和神经元修复。因此，我们旨在强调嘌呤能信号与小胶质细胞的肌动蛋白驱动的机械运动之间的联系，以促进AD的迁移和炎症。