title: Inositol trisphosphate receptor Ca2+ release channels in neurological diseases.
abstract: The modulation of cytoplasmic Ca2+ concentration by release from internal stores through the inositol trisphosphate receptor (InsP3R) Ca2+ release channel is a ubiquitous signaling system involved in the regulation of numerous processes. Because of its ubiquitous expression and roles in regulating diverse cell physiological processes, it is not surprising that the InsP3R has been implicated in a number of disease states. However, relatively few mutations in InsP3R genes have been identified to date. Here, I will discuss mutations in the type 1 InsP3R that have been discovered by analyses of human patients and mice with neurological disorders. In addition, I will highlight diseases caused by mutations in other genes, including Huntington's and Alzheimer's diseases and some spinocerebellar ataxias, where the mutant proteins have been found to exert strong influences on InsP3R function that may link InsP3R to disease pathogenesis.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, B39 Anatomy-Chemistry Bldg., 414 Guardian Dr., Philadelphia, PA 19104, USA. foskett@mail.med.upenn.edu
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Foskett
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D020754:Spinocerebellar Ataxias / Q000503:physiopathology; D002256:Carbonic Anhydrases; D047908:Intracellular Signaling Peptides and Proteins
chemical_list: D014408:Biomarkers, Tumor; D002118:Calcium; D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; C512818:CA8 protein, human; D002256:Carbonic Anhydrases; D047908:Intracellular Signaling Peptides and Proteins
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