Microglial phagocytosis of neurons in neurodegeneration, and its regulation. Issue 3 (17th March 2021)

• Record Type: Journal Article
• Authors: Butler, Claire A.; Popescu, Alma S.; Kitchener, Emily J. A.; Allendorf, David H.; Puigdellívol, Mar; Brown, Guy C.
• Is Part Of: Journal of neurochemistry. Volume 158:Issue 3(2021)
• Page Start: 621
• Page End: 639
• Publication Date: 2021-03-17
• Subjects: ageing -- Alzheimer's disease -- microglia -- neurodegeneration -- neuroinflammation -- Parkinson's disease -- phagocytosis; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.15327
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: 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. Abstract : Microglia are the brain's main phagocytes and can phagocytose both live and dead neurons, as well as synapses, dendrites and axons. We review here how this microglial phagocytosis is regulated, and the evidence that microglial phagocytosis of live neurons and synapses may contribute to neurodegeneration. During neurodegenerative disease, neurons, dendrites or synapses may become stressed by aggregated proteins, neuroinflammation, oxidants, energy depletion or excitotoxicity, resulting in release of opsonins, find‐me and eat‐me signals, inducing their phagocytosis by activated microglia. Thus, blocking this signalling and phagocytosis may help prevent neurodegeneration.