Vitamin D is a
hormone with both genomic and non-genomic actions. It exerts its activity by binding
vitamin D receptor (VDR), which belongs to the superfamily of
nuclear receptors and
ligand-activated
transcription factors. Since VDR has been found in various tissues, it has been estimated that it regulates approximately 3% of the human genome. Several recent studies have shown pleiotropic effects of
vitamin D in various processes such as cellular proliferation, differentiation, DNA repair and apoptosis and its involvement in different pathophysiological conditions as
inflammation,
diabetes mellitus, and
anemia. It has been suggested that
vitamin D could play an important role in neurodegenerative and cardiovascular disorders. Moderate to strong associations between lower serum
vitamin D concentrations and
stroke and cardiovascular events have been identified in different analytic approaches, even after controlling for traditional demographic and lifestyle covariates. The mechanisms behind the associations between
vitamin D and cerebrovascular and cardiologic profiles have been widely examined both in animal and human studies. Optimization of
vitamin D levels in human subjects may improve
insulin sensitivity and beta-cell function and lower levels of inflammatory markers. Moreover, it has been demonstrated that altered gene expression of VDR and 1,25D3-membrane-associated rapid response
steroid-binding (1,25D3-MARRS) receptor influences the role of
vitamin D within neurons and allows them to be more prone to degeneration. This review summarizes the current understanding of the molecular mechanisms underlying
vitamin D signaling and the consequences of
vitamin D deficiency in neurodegenerative and cardiovascular disorders.