Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation
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. Beside...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/18/12/2764 |
| id |
doaj-23c1e2324b8a4570a392a990f213054b |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Marcus O. W. Grimm Andrea Thiel Anna A. Lauer Jakob Winkler Johannes Lehmann Liesa Regner Christopher Nelke Daniel Janitschke Céline Benoist Olga Streidenberger Hannah Stötzel Kristina Endres Christian Herr Christoph Beisswenger Heike S. Grimm Robert Bals Frank Lammert Tobias Hartmann |
| spellingShingle |
Marcus O. W. Grimm Andrea Thiel Anna A. Lauer Jakob Winkler Johannes Lehmann Liesa Regner Christopher Nelke Daniel Janitschke Céline Benoist Olga Streidenberger Hannah Stötzel Kristina Endres Christian Herr Christoph Beisswenger Heike S. Grimm Robert Bals Frank Lammert Tobias Hartmann Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation International Journal of Molecular Sciences vitamin D vitamin D analogues amyloid precursor protein amyloid-β secretases Aβ-degradation |
| author_facet |
Marcus O. W. Grimm Andrea Thiel Anna A. Lauer Jakob Winkler Johannes Lehmann Liesa Regner Christopher Nelke Daniel Janitschke Céline Benoist Olga Streidenberger Hannah Stötzel Kristina Endres Christian Herr Christoph Beisswenger Heike S. Grimm Robert Bals Frank Lammert Tobias Hartmann |
| author_sort |
Marcus O. W. Grimm |
| title |
Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation |
| title_short |
Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation |
| title_full |
Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation |
| title_fullStr |
Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation |
| title_full_unstemmed |
Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation |
| title_sort |
vitamin d and its analogues decrease amyloid-β (aβ) formation and increase aβ-degradation |
| publisher |
MDPI AG |
| series |
International Journal of Molecular Sciences |
| issn |
1422-0067 |
| publishDate |
2017-12-01 |
| description |
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. |
| topic |
vitamin D vitamin D analogues amyloid precursor protein amyloid-β secretases Aβ-degradation |
| url |
https://www.mdpi.com/1422-0067/18/12/2764 |
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doaj-23c1e2324b8a4570a392a990f213054b2020-11-25T00:56:09ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-12-011812276410.3390/ijms18122764ijms18122764Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-DegradationMarcus O. W. Grimm0Andrea Thiel1Anna A. Lauer2Jakob Winkler3Johannes Lehmann4Liesa Regner5Christopher Nelke6Daniel Janitschke7Céline Benoist8Olga Streidenberger9Hannah Stötzel10Kristina Endres11Christian Herr12Christoph Beisswenger13Heike S. Grimm14Robert Bals15Frank Lammert16Tobias Hartmann17Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyDepartment of Psychiatry and Psychotherapy, Clinical Research Group, University Medical Centre Johannes Gutenberg, University of Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, GermanyDepartment of Internal Medicine V–Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyDepartment of Internal Medicine V–Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyDepartment of Internal Medicine V–Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyDepartment of Internal Medicine II–Gastroenterology, Saarland University Hospital, Saarland University, Kirrberger Str. 100, 66421 Homburg/Saar, GermanyExperimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, GermanyAlzheimer’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.https://www.mdpi.com/1422-0067/18/12/2764vitamin Dvitamin D analoguesamyloid precursor proteinamyloid-βsecretasesAβ-degradation |