title: Inflammasomes as therapeutic targets for Alzheimer's disease.
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.
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Claire S
authors.initials: CS
authors.lastname: White
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Lawrence
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Brough
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Rivers-Auty
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D007249:Inflammation / Q000473:pathology*; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D017628:Microglia / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
keywords: Alzheimer's disease; inflammasomes; inflammation