Please use this identifier to cite or link to this item: doi:10.22028/D291-27490
Title: Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation
Author(s): Grimm, Marcus O. W.
Thiel, Andrea
Lauer, Anna A.
Winkler, Jakob
Lehmann, Johannes
Regner, Liesa
Nelke, Christopher
Janitschke, Daniel
Benoist, Celine
Streidenberger, Olga
Stötzel, Hannah
Endres, Kristina
Herr, Christian
Beisswenger, Christoph
Grimm, Heike S.
Bals, Robert
Lammert, Frank
Hartmann, Tobias
Language: English
Title: International Journal of Molecular Sciences
Volume: 18
Issue: 12
Publisher/Platform: MDPI
Year of Publication: 2017
Free key words: vitamin D
vitamin D analogues
amyloid precursor protein
amyloid-β; secretases
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Alzheimer’s disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed. However, the exact underlying mechanisms remain to be elucidated and nothing is known about the potential effect of vitamin D analogues. Here we systematically investigate the effect of vitamin D and therapeutically used analogues (maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol) on AD-relevant mechanisms. D2 and D3 analogues decreased Aβ-production and increased Aβ-degradation in neuroblastoma cells or vitamin D deficient mouse brains. Effects were mediated by affecting the Aβ-producing enzymes BACE1 and γ-secretase. A reduced secretase activity was accompanied by a decreased BACE1 protein level and nicastrin expression, an essential component of the γ-secretase. Vitamin D and analogues decreased β-secretase activity, not only in mouse brains with mild vitamin D hypovitaminosis, but also in non-deficient mouse brains. Our results further strengthen the link between AD and vitamin D, suggesting that supplementation of vitamin D or vitamin D analogues might have beneficial effects in AD prevention.
DOI of the first publication: 10.3390/ijms18122764
Link to this record: urn:nbn:de:bsz:291--ds-274905
hdl:20.500.11880/28598
http://dx.doi.org/10.22028/D291-27490
ISSN: 1422-0067
Date of registration: 17-Jan-2020
Description of the related object: Supplementary Material
Related object: https://www.mdpi.com/1422-0067/18/12/2764/s1
Faculty: M - Medizinische Fakultät
Department: M - Innere Medizin
M - Neurologie und Psychiatrie
Professorship: M - Prof. Dr. Tobias Hartmann
M - Prof. Dr. Frank Lammert
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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