Axe Neurosciences, Centre de Recherche du CHU de Québec, Université Laval, Quebec, QC, Canada.
Département de Médecine Moléculaire, Faculté de Médecine, Université Laval, Quebec, QC, Canada.
Mol Neurodegener. 2019 Apr 5;14(1):16. doi: 10.1186/s13024-019-0314-8.
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.
一个新兴的观点表明，神经胶质细胞丧失有益功能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具有吞噬作用，可吞噬突触、凋亡细胞、细胞碎片和释放的毒性蛋白。由于致病性蛋白的积累是帕金森病 (PD) 的一个关键特征，吞噬清除功能受损可能参与 PD 的发病机制。相比之下，增强的、不受控制的和潜在有毒的神经胶质细胞清除能力可能导致突触退化。在这里，我们总结了小胶质细胞和星形胶质细胞吞噬作用的分子机制的最新知识，重点介绍了吞噬功能障碍在神经元变性中的可能意义。几种在 PD 中显示遗传变异的内溶酶体蛋白在小胶质细胞和星形胶质细胞中高度表达。我们还提出了溶酶体缺陷可能影响吞噬清除的证据，并讨论了在 PD 中恢复或增强溶酶体功能的治疗相关性。
