Gezen-Ak Duygu, Dursun Erdinc
Department of Neuroscience, Brain and Neurodegenerative Disorders Research Laboratories, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey.
J Alzheimers Dis. 2023;95(4):1273-1299. doi: 10.3233/JAD-230214.
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.
维生素D是一种具有神经甾体样特性的甾醇类激素。其广为人知的核激素受体,即维生素D受体,最近被提议作为一种线粒体转录因子,发挥其主要功能。第二种受体是一种内质网蛋白,蛋白质二硫键异构酶A3(PDIA3),被认为可发挥快速反应作用。维生素D对多种系统有影响,尤其是通过钙代谢。其中,在我们所讨论的主题背景下,神经系统占有重要地位。最近的研究表明,维生素D及其受体对神经系统有诸多影响。神经退行性变是一个长期过程。在人的整个生命周期中,维生素D缺乏也是如此。我们之前的研究以及其他研究表明,长期维生素D缺乏(维生素D缺乏症或维生素D利用效率低下)的结果可能会使神经元易受衰老和神经退行性变的影响。我们建议,在考虑基于维生素D的干预研究时,在生命的各个阶段将维生素D水平维持在适当水平,考虑使用能激活维生素D受体的激动剂等新方法,并利用紫外线B合成过程中产生的其他衍生物至关重要。鉴于维生素D的大多数方面,本综述概述了维生素D及其受体如何发挥作用以及与神经退行性变的关系,重点强调了阿尔茨海默病。