The neuroprotective effect of vitamin D in Parkinson's disease: association or causation

Parkinson's disease (PD) is a chronic neurodegenerative disease (NDD) due to the degeneration of dopaminergic neurons (DNs) in the substantia nigra (SN). PD is characterized by diverse motor symptoms such as rigidity, resting tremors, and bradykinesia, and non-motor symptoms such as cognitive dysfunction and sleep disturbances. Vitamin D (VD), VD receptor (VDR), and VD metabolites are present in the brain and play a role in maintaining the development, differentiation, and functions of the DNs. VDRs exert protective effects against PD neuropathology by modulating functional capacity and DNs neurotransmission in the SN. In virtue of its anti-inflammatory and antioxidant activities, VD could be effective in the prevention and treatment of PD. VD exerts a neuroprotective effect by reducing oxidative stress and mitochondrial dysfunction, and by increasing autophagy and brain-derived neurotrophic factor (BDNF). Low VD serum level is connected with cognitive dysfunction and the development of dementia in PD. The VD-mediated cognitive augmenting effect is interrelated to the safeguarding of synaptic plasticity and modulation of neurotransmitter release. VD deficiency is linked with the severity of olfactory dysfunction which precedes the progression of symptomatic PD. However, the precise role of VD in PD remains unidentified, and there is a conflict about whether treatment with VD can ameliorate PD or not.