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RNA\u2010seq and genome\u2010wide association (GWAS) studies have linked multiple phagocytic genes to neurodegenerative diseases, and knock\u2010out 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\u20103, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15327-fig-0004-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.15327","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T03:06:47Z","timestamp":1613790407000},"page":"621-639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":294,"title":["Microglial phagocytosis of neurons in neurodegeneration, and its regulation"],"prefix":"10.1111","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9320-8297","authenticated-orcid":false,"given":"Claire A.","family":"Butler","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9459-6754","authenticated-orcid":false,"given":"Alma S.","family":"Popescu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J. 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