title: Microglial priming in neurodegenerative disease.
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.
authors.affiliation: Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Tremona Road, Southampton SO16 6YD, UK.
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D002493:Central Nervous System Diseases / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008262:Macrophage Activation; D017628:Microglia / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000473:pathology* / Q000628:therapy
chemical_list: D000893:Anti-Inflammatory Agents