title: Vitamin D: a custodian of cell signalling stability in health and disease.
abstract: There is increasing evidence that a deficiency in vitamin D contributes to many human diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), hypertension and cardiovascular disease. The ability of vitamin D to maintain healthy cells seems to depend on its role as a guardian of phenotypic stability particularly with regard to the reactive oxygen species (ROS) and Ca2+ signalling systems. Vitamin D maintains the expression of those signalling components responsible for stabilizing the low-resting state of these two signalling pathways. This vitamin D signalling stability hypothesis proposes that vitamin D, working in conjunction with klotho and Nrf2 (nuclear factor-erythroid-2-related factor 2), acts as a custodian to maintain the normal function of the ROS and Ca2+ signalling pathways. A decline in vitamin D levels will lead to an erosion of this signalling stability and may account for why so many of the major diseases in man, which have been linked to vitamin D deficiency, are associated with a dysregulation in both ROS and Ca2+ signalling.
authors.affiliation: *The Babraham Institute, Babraham, Cambridge, CB22 3AT, U.K.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Berridge
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020013:Calcium Signaling / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000090265:Klotho Proteins; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014807:Vitamin D / Q000235:genetics* / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D014807:Vitamin D; D005966:Glucuronidase; D000090265:Klotho Proteins