Neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, and Huntington's disease, represent unmet medical and social needs. Still, no definitive cure exists for these illnesses, hence a therapeutic approach with molecules able to prevent/downtone/modify the disease seems highly attractive. Remarkably, a higher risk of neurodegenerative disease is associated with low vitamin D levels. Vitamin D is a multifaceted molecule able to target critical neuroinflammatory processes underlying neurodegeneration, acting through genomic or rapid signaling. This narrative review aims to focus on vitamin D's potential to be an optimal neuroprotective molecule, based on its ability to target and counteract aberrant biomolecular processes involved in neuroinflammation/neurodegeneration. Noticeably, exercise can potentiate vitamin D's protective effect through some anti-inflammatory actions exerted on shared biomolecular targets. Thus, although vitamin D is not strictly a drug, it could be potentially allocated within the therapeutic approach to neurodegenerative diseases in combination with adapted exercise, best as an early intervention. Topics on the complexity concerning the doses for supplementation and data discrepancy from trials are addressed. The urgent demand is to test and clarify vitamin D efficacy and safety, combined or not with exercise, in clinical settings.
Keywords: exercise; neurodegeneration; neuroinflammation; vitamin D.