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Article type: Research Article
Authors: Gezen-Ak, Duygu; * | Yılmazer, Selma | Dursun, Erdinç; *
Affiliations: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
Correspondence: [*] Correspondence to: Erdinç Dursun and Duygu Gezen-Ak, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, 34098 Istanbul, Turkey. Tel.: +90 212 414 30 00/21627/+90 533 339 98 82; Fax: +90 212 414 30 42; E-mails: [email protected]; [email protected].
Abstract: Scientists have worked for over a century to uncover the basis of Alzheimer's disease (AD) with the ultimate goal of discovering a treatment. However, none of the approaches utilized have defined the exact cause of the disease or an ultimate treatment for AD. In this review, we aim to define the role of vitamin D in AD from a novel and fundamental perspective and attempt to answer the following question: Why should we seriously consider “simple” vitamin D as a “fundamental factor” in AD? To answer this question, we explain the protective effects of vitamin D in the central nervous system and how the action of vitamin D and AD-type pathology overlap. Furthermore, we suggest that the role of vitamin D in AD includes not only vitamin D deficiency and vitamin D-related genes but also the disruption of vitamin D metabolism and action. This suggestion is supported by evidence that the disruption of vitamin D pathways mimic amyloid pathology. We define the term “inefficient utilization of vitamin D” as any alteration in vitamin D-related genes, including receptors, the enzymes related to vitamin D metabolism or the transporters of vitamin D, and we discuss the potential correlation of vitamin D status with the vulnerability of neurons to aging and neurodegeneration. Finally, in addition to the current knowledge that defines AD, we suggest that AD could be the result of a long-term hormonal imbalance in which the critical hormone is vitamin D, a secosteroid that has long been misnamed.
Keywords: Alzheimer's disease, amyloid-β, calcium homeostasis, ERp57/1, 25-MARRS, haplotype, hormone imbalance, oxidative stress, VDR, vitamin D, vitamin D deficiency
DOI: 10.3233/JAD-131970
Journal: Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 257-269, 2014
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