title: Targeting TNF-α to elucidate and ameliorate neuroinflammation in neurodegenerative diseases.
abstract: Inflammatory signals generated within the brain and peripheral nervous system direct diverse biological processes. Key amongst the inflammatory molecules is tumor necrosis factor-α (TNF-α), a potent pro-inflammatory cytokine that, via binding to its associated receptors, is considered to be a master regulator of cellular cascades that control a number of diverse processes coupled to cell viability, gene expression, synaptic integrity and ion homeostasis. Whereas a self-limiting neuroinflammatory response generally results in the resolution of an intrinsically or extrinsically triggered insult by the elimination of toxic material or injured tissue to restore brain homeostasis and function, in the event of an unregulated reaction, where the immune response persists, inappropriate chronic neuroinflammation can ensue. Uncontrolled neuroinflammatory activity can induce cellular dysfunction and demise, and lead to a self-propagating cascade of harmful pathogenic events. Such chronic neuroinflammation is a typical feature across a range of debilitating common neurodegenerative diseases, epitomized by Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, in which TNF-α expression appears to be upregulated and may represent a valuable target for intervention. Elaboration of the protective homeostasis signaling cascades from the harmful pathogenic ones that likely drive disease onset and progression could aid in the clinical translation of approaches to lower brain and peripheral nervous system TNF-α levels, and amelioration of inappropriate neuroinflammation.
authors.affiliation: Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Frankola
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.forename: Weiming
authors.initials: W
authors.lastname: Luo
authors.forename: David
authors.initials: D
authors.lastname: Tweedie
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D002470:Cell Survival; D006801:Humans; D058990:Molecular Targeted Therapy; D009443:Neuritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D014409:Tumor Necrosis Factor-alpha