Nitric oxide and nitric oxide synthase in Huntington's disease.
Nitric oxide (NO) is a biologically active inorganic molecule produced when the semiessential amino acid l-arginine is converted to l-citrulline and NO via the enzyme nitric oxide synthase (NOS). NO is known to be involved in the regulation of many physiological processes, such as control of blood flow, platelet adhesion, endocrine function, neurotransmission, neuromodulation, and inflammation, to name only a few. During neuropathological conditions, the production of NO can be either protective or toxic, dependent on the stage of the disease, the isoforms of NOS involved, and the initial pathological event. This paper reviews the properties of NO and NOS and the pathophysiology of Huntington's disease (HD). It discusses ways in which NO and NOS may interact with the protein product of HD and reviews data implicating NOS in the neuropathology of HD. This is followed by a synthesis of current information regarding how NO/NOS may contribute to HD-related pathology and identification of areas for potential future research.
Deckel
A W
AW
Department of Psychiatry, Program in Neuroscience and Huntington's Disease Program, University of Connecticut Medical School, Farmington, Connecticut 03060-2103, USA. deckel@psychiatry.uchc.edu
D000818:Animals; D017209:Apoptosis; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D050882:CREB-Binding Protein; D002147:Calmodulin / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004789:Enzyme Activation; D004790:Enzyme Induction; D005544:Forecasting; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000172:deficiency / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015534:Trans-Activators / Q000378:metabolism
D002147:Calmodulin; C096896:HAP1 protein, human; C490758:Hap1 protein, mouse; D009419:Nerve Tissue Proteins; D009566:Nitrates; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C039642:peroxynitric acid; D009569:Nitric Oxide; D018698:Glutamic Acid; D001120:Arginine; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse; D020169:Caspases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)