Department of Biochemistry, University of Cambridge, Cambridge, UK.
Departament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
J Neurochem. 2021 Aug;158(3):621-639. doi: 10.1111/jnc.15327. Epub 2021 Mar 17.
There is growing evidence that excessive microglial phagocytosis of neurons and synapses contributes to multiple brain pathologies. RNA-seq and genome-wide association (GWAS) studies have linked multiple phagocytic genes to neurodegenerative diseases, and knock-out of phagocytic genes has been found to protect against neurodegeneration in animal models, suggesting that excessive microglial phagocytosis contributes to neurodegeneration. Here, we review recent evidence that microglial phagocytosis of live neurons and synapses causes neurodegeneration in animal models of Alzheimer's disease and other tauopathies, Parkinson's disease, frontotemporal dementias, multiple sclerosis, retinal degeneration and neurodegeneration induced by ischaemia, infection or ageing. We also review factors regulating microglial phagocytosis of neurons, including: nucleotides, frackalkine, phosphatidylserine, calreticulin, UDP, CD47, sialylation, complement, galectin-3, Apolipoprotein E, phagocytic receptors, Siglec receptors, cytokines, microglial epigenetics and expression profile. Some of these factors may be potential treatment targets to prevent neurodegeneration mediated by excessive microglial phagocytosis of live neurons and synapses.
越来越多的证据表明，过度的小胶质细胞吞噬神经元和突触会导致多种脑部病变。RNA-seq 和全基因组关联 (GWAS) 研究将多种吞噬基因与神经退行性疾病联系起来，并且发现吞噬基因的敲除可以在动物模型中预防神经退行性变，这表明过度的小胶质细胞吞噬作用会导致神经退行性变。在这里，我们回顾了最近的证据，表明小胶质细胞对活神经元和突触的吞噬作用会导致阿尔茨海默病和其他 tau 病、帕金森病、额颞叶痴呆、多发性硬化症、视网膜变性和缺血、感染或衰老引起的神经退行性变的动物模型中的神经退行性变。我们还回顾了调节小胶质细胞吞噬神经元的因素，包括核苷酸、 fractalkine、磷脂酰丝氨酸、钙网蛋白、UDP、CD47、唾液酸化、补体、半乳糖凝集素-3、载脂蛋白 E、吞噬受体、Siglec 受体、细胞因子、小胶质细胞表观遗传学和表达谱。其中一些因素可能是预防由活神经元和突触过度小胶质细胞吞噬引起的神经退行性变的潜在治疗靶点。
