title: Inflammasomes link vascular disease with neuroinflammation and brain disorders.
abstract: The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer's or Parkinson's disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales. However, the mechanisms through which inflammation impacts on neurological disease are improperly defined. To develop effective therapeutic approaches, it is imperative to understand how detrimental inflammatory processes could be blocked selectively, or controlled for prolonged periods, without compromising essential immune defence mechanisms. Increasing evidence indicates that common risk factors for brain disorders, such as atherosclerosis, diabetes, hypertension, obesity or infection involve the activation of NLRP3, NLRP1, NLRC4 or AIM2 inflammasomes, which are also associated with various neurological diseases. This review focuses on the mechanisms whereby inflammasomes, which integrate diverse inflammatory signals in response to pathogen-driven stimuli, tissue injury or metabolic alterations in multiple cell types and different organs of the body, could functionally link vascular- and neurological diseases and hence represent a promising therapeutic target.
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary.
authors.forename: Nikolett
authors.initials: N
authors.lastname: Lénárt
authors.affiliation: Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Brough
authors.affiliation: Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary denes.adam@koki.mta.hu.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Dénes
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D001927:Brain Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology*; D020078:Neurogenic Inflammation / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D014652:Vascular Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D058847:Inflammasomes
keywords: Inflammation; brain disease; inflammasome; neurodegeneration; systemic