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Microglial priming in neurodegenerative disease

Microglial priming in neurodegenerative disease
Microglial priming in neurodegenerative disease
Under physiological conditions, the number and function of microglia-the resident macrophages of the CNS-is tightly controlled by the local microenvironment. In response to neurodegeneration and the accumulation of abnormally folded proteins, however, microglia multiply and adopt an activated state-a process referred to as priming. Studies using preclinical animal models have shown that priming of microglia is driven by changes in their microenvironment and the release of molecules that drive their proliferation. Priming makes the microglia susceptible to a secondary inflammatory stimulus, which can then trigger an exaggerated inflammatory response. The secondary stimulus can arise within the CNS, but in elderly individuals, the secondary stimulus most commonly arises from a systemic disease with an inflammatory component. The concept of microglial priming, and the subsequent exaggerated response of these cells to secondary systemic inflammation, opens the way to treat neurodegenerative diseases by targeting systemic disease or interrupting the signalling pathways that mediate the CNS response to systemic inflammation. Both lifestyle changes and pharmacological therapies could, therefore, provide efficient means to slow down or halt neurodegeneration

Perry, V. Hugh
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Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96

Perry, V. Hugh and Holmes, Clive (2014) Microglial priming in neurodegenerative disease. Nature Reviews Neurology. (doi:10.1038/nrneurol.2014.38).

Record type: Article

Abstract

Under physiological conditions, the number and function of microglia-the resident macrophages of the CNS-is tightly controlled by the local microenvironment. In response to neurodegeneration and the accumulation of abnormally folded proteins, however, microglia multiply and adopt an activated state-a process referred to as priming. Studies using preclinical animal models have shown that priming of microglia is driven by changes in their microenvironment and the release of molecules that drive their proliferation. Priming makes the microglia susceptible to a secondary inflammatory stimulus, which can then trigger an exaggerated inflammatory response. The secondary stimulus can arise within the CNS, but in elderly individuals, the secondary stimulus most commonly arises from a systemic disease with an inflammatory component. The concept of microglial priming, and the subsequent exaggerated response of these cells to secondary systemic inflammation, opens the way to treat neurodegenerative diseases by targeting systemic disease or interrupting the signalling pathways that mediate the CNS response to systemic inflammation. Both lifestyle changes and pharmacological therapies could, therefore, provide efficient means to slow down or halt neurodegeneration

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More information

e-pub ahead of print date: March 2014
Organisations: Biomedicine, Centre for Biological Sciences

Identifiers

Local EPrints ID: 364110
URI: http://eprints.soton.ac.uk/id/eprint/364110
PURE UUID: bbc8fad6-f99b-44de-8052-ffd5436a71f1
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

Catalogue record

Date deposited: 04 Apr 2014 14:01
Last modified: 17 Dec 2019 01:54

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