Vitamin D and neurodegenerative diseases

Abstract

Neurodegenerative diseases, featured by progressive loss of structure or function of neurons, are considered incurable at present. Movement disorders like tremor and postural instability, cognitive or behavioral disorders such as memory impairment are the most common symptoms of them and the growing patient population of neurodegenerative diseases poses a serious threat to public health and a burden on economic development. Hence, it is vital to prevent the occurrence of the diseases and delay their progress. Vitamin D can be transformed into a hormone in vivo with both genomic and non-genomic actions, exerting diverse physiological effects. Cumulative evidence indicates that vitamin D can ameliorate neurodegeneration by regulating pertinent molecules and signaling pathways including maintaining Ca²⁺ homeostasis, reducing oxidative stress, inhibiting inflammation, suppressing the formation and aggregation of the pathogenic protein, etc. This review updates discoveries of molecular mechanisms underlying biological functions of vitamin D in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and vascular dementia. Clinical trials investigating the influence of vitamin D supplementation in patients with neurodegenerative diseases are also summarized. The synthesized information will probably provoke an enhanced understanding of the neuroprotective roles of vitamin D in the nervous system and provide therapeutic options for patients with neurodegenerative diseases in the future.

Keywords: AD, Alzheimer’s disease; Alzheimer’s disease; MS, multiple sclerosis; Multiple sclerosis; Neurodegenerative disease; PD, Parkinson’s disease; Parkinson’s disease; SVD, small vessel disease; VDBP, vitamin D binding protein; VDR, vitamin D receptors; VaD, vascular dementia; Vitamin D.

Fig. 1

The biosynthesis, metabolism, and mechanism of action of vitamin D. VDBP, vitamin D binding protein; RXR, retinoid X receptor; VDR, vitamin D receptor; 1,25D₃-MARRS, 1,25D₃ membrane-associated rapid-response steroid-binding protein; VDRE, vitamin D-responsive elements.

Fig. 2

The functions of vitamin D. ↑: up-regulate; ↓: down-regulate; +: positive influence in; -: negative influence in. DC, dendritic cells; Th, T helper; iNOS, inducible nitric oxide synthase; GDNF, glial-line derived neurotrophic factors; SMC, smooth muscle cells; Aβ, beta-amyloid; P-gp, P-glycoprotein; TNF-α, tumor necrosis factor alpha; eNO, endothelial NO; VCAM-1, vascular cell adhesion molecule 1; VE-cadherin, vascular endothelial cadherin; M-CSF, macrophage colony stimulating factor; IL, interleukin; ZO-1, zonula occludin-1.