Microglial phagocytosis of neurons in neurodegeneration, and its regulation.
Kitchener, Emily JA
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Butler, C. A., Popescu, A. S., Kitchener, E. J., Allendorf, D. H., Puigdellívol, M., & Brown, G. C. (2021). Microglial phagocytosis of neurons in neurodegeneration, and its regulation.. J Neurochem, 158 (3), 621-639. https://doi.org/10.1111/jnc.15327
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.
Medical Research Council (MR/L010593/1)
European Commission Horizon 2020 (H2020) Research Infrastructures (RI) (115976)
Biotechnology and Biological Sciences Research Council (BB/R506047/1)
Biotechnology and Biological Sciences Research Council (1645643)
External DOI: https://doi.org/10.1111/jnc.15327
This record's URL: https://www.repository.cam.ac.uk/handle/1810/318317
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