Vitamin D, a Secosteroid Hormone and Its Multifunctional Receptor, Vitamin D Receptor, in Alzheimer’s Type Neurodegeneration

Article type: Review Article

Authors: Gezen-Ak, Duygu^{; *} | Dursun, Erdinc^{; *}

Affiliations: Department of Neuroscience, Brain and Neurodegenerative Disorders Research Laboratories, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey

Correspondence: [*] Correspondence to: Duygu Gezen-Ak and Erdinc Dursun, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey. Tel.: +90 212 414 30 00/22032, +90 533 339 98 82; E-mails: [email protected] and [email protected]; ORCID: 0000-0001-7611-2111, 0000-0003-3701-6674

Abstract: Vitamin D is a secosteroid hormone exerting neurosteroid-like properties. Its well-known nuclear hormone receptor, and recently proposed as a mitochondrial transcription factor, vitamin D receptor, acts for its primary functions. The second receptor is an endoplasmic reticulum protein, protein disulfide isomerase A3 (PDIA3), suggested to act as a rapid response. Vitamin D has effects on various systems, particularly through calcium metabolism. Among them, the nervous system has an important place in the context of our subject. Recent studies have shown that vitamin D and its receptors have numerous effects on the nervous system. Neurodegeneration is a long-term process. Throughout a human life span, so is vitamin D deficiency. Our previous studies and others have suggested that the out-come of long-term vitamin D deficiency (hypovitaminosis D or inefficient utilization of vitamin D), may lead neurons to be vulnerable to aging and neurodegeneration. We suggest that keeping vitamin D levels at adequate levels at all stages of life, considering new approaches such as agonists that can activate vitamin D receptors, and utilizing other derivatives produced in the synthesis process with UVB are crucial when considering vitamin D-based intervention studies. Given most aspects of vitamin D, this review outlines how vitamin D and its receptors work and are involved in neurodegeneration, emphasizing Alzheimer’s disease.

Keywords: Alzheimer’s disease, mitochondria, neurodegeneration, vitamin D, vitamin D receptor

DOI: 10.3233/JAD-230214

Journal: Journal of Alzheimer's Disease, vol. 95, no. 4, pp. 1273-1299, 2023