title: Vitamin D cell signalling in health and disease.
abstract: Vitamin D deficiency has been linked to many human diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), hypertension and cardiovascular disease. A Vitamin D phenotypic stability hypothesis, which is developed in this review, attempts to describe how this vital hormone acts to maintain healthy cellular functions. This role of Vitamin D as a guardian of phenotypic stability seems to depend on its ability to maintain the redox and Ca(2+) signalling systems. It is argued that its primary action is to maintain the expression of those signalling components responsible for stabilizing the low resting state of these two signalling pathways. This phenotypic stability role is facilitated through the ability of vitamin D to increase the expression of both Nrf2 and the anti-ageing protein Klotho, which are also major regulators of Ca(2+) and redox signalling. A decline in Vitamin D levels will lead to a decline in the stability of this regulatory signalling network 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 Ca(2+) signalling.
authors.affiliation: The Babraham Institute, Babraham, Cambridge CB22 3AT, United Kingdom. Electronic address: michael.berridge@babraham.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Berridge
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*; D014813:Vitamin K Deficiency / Q000150:complications / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D014807:Vitamin D; D002118:Calcium
keywords: Alzheimer's disease; Calcium; Parkinson's disease; Reactive oxygen species; Schizophrenia; Vitamin D