title: Chronic Brain Inflammation: The Neurochemical Basis for Drugs to Reduce Inflammation.
abstract: It is now recognised that the brain and the peripheral immune system have bidirectional communication in both health and neuronal diseases. Brain inflammation results after both acute injury and also with the appearance of mutated proteins or endogenous neurotoxic metabolites associated with slow neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and some psychiatric disorders. Microglia play a key role in brain inflammation by the release of pro-inflammatory cytokines and with ageing, microglia exhibit 'priming' leading to increased basal release of the pro-inflammatory cytokines. Neurochemical targets to reduce or slow chronic brain inflammation include cyclooxygenase enzymes, Nrf2 transcription factor, angiotensin AT1 receptors and sigma-1 receptors. Development of more selective drugs to act at these targets is occurring but large scale clinical trials to validate the drugs will take significant time.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. bevyn.jarrott@florey.edu.au.
authors.forename: Bevyn
authors.initials: B
authors.lastname: Jarrott
authors.affiliation: Bio 21 Institute and School of Chemistry, The University of Melbourne, Victoria, 3010, Australia.
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Williams
mesh_terms: D000375:Aging / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines
keywords: Angiotensin AT1 receptor antagonists; Brain inflammation; Chronic neurodegenerative diseases; Cyclooxygenase inhibitors; Cytokines; Microglia; Sigma-1 receptors