title: Redox regulation of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases.
abstract: The loss or injury of neurons associated with oxidative and nitrosative redox stress plays an important role in the onset of various neurodegenerative diseases. Specifically, nitric oxide (NO), can affect neuronal survival through a process called S-nitrosylation, by which the NO group undergoes a redox reaction with specific protein thiols. This in turn can lead to the accumulation of misfolded proteins, which generally form aggregates in Alzheimer's, Parkinson's, and other neurodegenerative diseases. Evidence suggests that S-nitrosylation can also impair mitochondrial function and lead to excessive fission of mitochondria and consequent bioenergetic compromise via effects on the activity of the fission protein dynamin-related protein 1 (Drp1). This insult leads to synaptic dysfunction and loss. Additionally, high levels of NO can S-nitrosylate a number of aberrant targets involved in neuronal survival pathways, including the antiapoptotic protein XIAP, inhibiting its ability to prevent apoptosis.
authors: Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Tomohiro
authors: T
authors: Nakamura
authors: Dong-Hyung
authors: DH
authors: Cho
authors: Stuart A
authors: SA
authors: Lipton
mesh_terms: D000818:Animals; D020169:Caspases / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D028361:Mitochondrial Diseases / Q000503:physiopathology*; D018832:Molecular Chaperones / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000503:physiopathology; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D009603:Nitroso Compounds; D009569:Nitric Oxide; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D020169:Caspases