An emerging picture suggests that glial cells’ loss of beneficial roles or gain of toxic functions can contribute to neurodegenerative conditions. Among glial cells, microglia and astrocytes have been shown to play phagocytic roles by engulfing synapses, apoptotic cells, cell debris, and released toxic proteins. As pathogenic protein accumulation is a key feature in Parkinson’s disease (PD), compromised phagocytic clearance might participate in PD pathogenesis. In contrast, enhanced, uncontrolled and potentially toxic glial clearance capacity could contribute to synaptic degeneration. Here, we summarize the current knowledge of the molecular mechanisms underlying microglial and astrocytic phagocytosis, focusing on the possible implication of phagocytic dysfunction in neuronal degeneration. Several endo-lysosomal proteins displaying genetic variants in PD are highly expressed by microglia and astrocytes. We also present the evidence that lysosomal defects can affect phagocytic clearance and discuss the therapeutic relevance of restoring or enhancing lysosomal function in PD.

中文翻译：

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帕金森病中的神经胶质吞噬细胞清除

最新的研究表明，神经胶质细胞失去有益作用或获得毒性功能可能导致神经退行性疾病。在神经胶质细胞中，小胶质细胞和星形胶质细胞已被证明通过吞噬突触、凋亡细胞、细胞碎片和释放的有毒蛋白质来发挥吞噬作用。由于致病蛋白积累是帕金森病 (PD) 的一个关键特征，因此吞噬细胞清除功能受损可能参与帕金森病的发病机制。相反，增强的、不受控制的和潜在有毒的胶质细胞清除能力可能会导致突触退化。在这里，我们总结了目前对小胶质细胞和星形细胞吞噬作用分子机制的了解，重点关注吞噬功能障碍在神经元变性中的可能含义。PD 中表现出遗传变异的几种内溶酶体蛋白在小胶质细胞和星形胶质细胞中高度表达。我们还提供了溶酶体缺陷可以影响吞噬细胞清除的证据，并讨论了恢复或增强 PD 溶酶体功能的治疗相关性。