Vitamin D, Cell Signalling Phenotypic Stability and Alzheimer’s Disease

Mini Review

Austin J Clin Neurol 2015;2(3): 1033.

Vitamin D, Cell Signalling Phenotypic Stability and Alzheimer’s Disease

Berridge MJ*

Laboratory of Molecular Signalling, Babraham Research Campus, UK

*Corresponding author: Berridge MJ, Laboratory of Molecular Signalling, the Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK

Received: March 04, 2015; Accepted: March 25, 2015; Published: April 07, 2015


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 Ca2+ 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-aging protein Klotho, which are also major regulators of Ca2+ 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 Ca2+ signalling as is described for Alzheimer’s disease (AD).

Keywords: Vitamin D; Calcium; Klotho; Nrf2; Alzheimer’s disease


Vitamin D deficiency is a major human epidemic [1]. There is increasing evidence for a link between Vitamin D deficiency and many of the major human diseases (Figure 1). While the evidence for such associations is strong, particularly in the case of neural diseases such as Alzheimer’s disease, Parkinson’s disease and Multiple Sclerosis (MS), there is little information as to why a deficiency in Vitamin D can have such serious consequences. In an attempt to answer this question, I have developed a Vitamin D phenotypic stability hypothesis that sets out to explain why Vitamin D is such an important hormone responsible for maintaining normal cellular functions [2].