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Inflammasomes as therapeutic targets for Alzheimer's disease

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White, CS, Lawrence, CB, Brough, D and Rivers-Auty, J ORCID: 0000-0001-5321-2347 2017 , 'Inflammasomes as therapeutic targets for Alzheimer's disease' , Brain Pathology, vol. 27, no. 2 , pp. 223-234 , doi: 10.1111/bpa.12478.

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Abstract

Alzheimer's disease is the most common form of progressive dementia, typified initially by short term memory deficits which develop into a dramatic global cognitive decline. The classical hall marks of Alzheimer's disease include the accumulation of amyloid oligomers and fibrils, and the intracellular formation of neurofibrillary tangles of hyperphosphorylated tau. It is now clear that inflammation also plays a central role in the pathogenesis of the disease through a number of neurotoxic mechanisms. Microglia are the key immune regulators of the CNS which detect amyloidopathy through cell surface and cytosolic pattern recognition receptors (PRRs) and respond by initiating inflammation through the secretion of cytokines such as interleukin-1β (IL-1β). Inflammasomes, which regulate IL-1β release, are formed following activation of cytosolic PRRs, and using genetic and pharmacological approaches, NLRP3 and NLRP1 inflammasomes have been found to be integral in pathogenic neuroinflammation in animal models of Alzheimer's disease. Therefore, the inflammasomes are very promising novel pharmacological targets which merit further research in the continued endeavor for efficacious therapeutics for Alzheimer's disease.

Item Type: Article
Authors/Creators:White, CS and Lawrence, CB and Brough, D and Rivers-Auty, J
Keywords: Alzheimer's disease, NSAID, inflammation, NLRP3
Journal or Publication Title: Brain Pathology
Publisher: Int Soc Neuropathology
ISSN: 1015-6305
DOI / ID Number: 10.1111/bpa.12478
Copyright Information:

Copyright 2016 International Society of Neuropathology. This is the peer reviewed version of the following article: White, C. S., Lawrence, C. B., Brough, D., Rivers-Auty, J., 2017. Inflammasomes as therapeutic targets for Alzheimer's disease, Brain Pathology, 27(2), 223-234 which has been published in final form at https://doi.org/10.1111/bpa.12478. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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