Microglial phagocytosis of neurons in neurodegeneration, and its regulation

Butler, Claire A.; Popescu, Alma S.; Kitchener, Emily J. A.; Allendorf, David H.; Puigdellívol, Mar; Brown, Guy C.

doi:10.1111/jnc.15327

Cited by 295

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Microglial phagocytosis of neurons in neurodegeneration, and its regulation

Butler, Claire A., Popescu, Alma S., Kitchener, Emily J. A., Allendorf, David H., Puigdellívol, Mar, Brown, Guy C.·2021·Journal of Neurochemistry

DOI 10.1111/jnc.15327

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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. image

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Soluble factors secreted by activated microglia under chronic inflammation are thought to mediate aberrant synaptic phagocytosis inducing synapse loss and cognitive impairment.
“Soluble factors secreted by activated microglia under conditions of chronic inflammation have been thought to mediate aberrant synaptic phagocytosis inducing synapse loss and cognitive impairment (Butler et al., 2021; Dejanovic et al., 2018).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Butler et al., 2021

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Authors: Butler, C. A., Popescu, A. S., Kitchener, E. J. A., Allendorf, D. H., Puigdellívol, M., & Brown, G. C.
Affiliations: Department of Biochemistry University of Cambridge Cambridge UK
ORCID: Butler, Claire A.
Popescu, Alma S.
Allendorf, David H.
Puigdellívol, Mar
Brown, Guy C.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2021-03-17
Volume: 158
Issue: 3
Pages: 621-639
ISSN: 0022-3042
1471-4159
DOI: 10.1111/jnc.15327
Cited by: 295
References: 50
Language: en
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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Microglial phagocytosis of neurons in neurodegeneration, and its regulation

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