Please use this identifier to cite or link to this item: doi:10.22028/D291-32387
Title: The impact of capsaicinoids on APP processing in Alzheimer's disease in SH-SY5Y cells
Author(s): Grimm, Marcus O.W.
Blümel, Tamara
Lauer, Anna A.
Janitschke, Daniel
Stahlmann, Christoph
Mett, Janine
Haupenthal, Viola J.
Miederer, Anna-Maria
Niemeyer, Barbara A.
Grimm, Heike S.
Hartmann, Tobias
Language: English
Title: Scientific Reports
Volume: 10
Issue: 1
Publisher/Platform: SpringerNature
Year of Publication: 2020
Free key words: Biochemistry
Diseases
Medical research
Molecular biology
Molecular medicine
Neurology
Neuroscience
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: The vanilloid capsaicin is a widely consumed spice, known for its burning and "hot" sensation through activation of TRPV1 ion-channels, but also known to decrease oxidative stress, inflammation and influence tau-pathology. Beside these positive effects, little is known about its effects on amyloid-precursor-protein (APP) processing leading to amyloid-β (Aβ), the major component of senile plaques. Treatment of neuroblastoma cells with capsaicinoids (24 hours, 10 µM) resulted in enhanced Aβ-production and reduced Aβ-degradation, leading to increased Aβ-levels. In detailed analysis of the amyloidogenic-pathway, both BACE1 gene-expression as well as protein-levels were found to be elevated, leading to increased β-secretase-activity. Additionally, γ-secretase gene-expression as well as activity was enhanced, accompanied by a shift of presenilin from non-raft to raft membrane-domains where amyloidogenic processing takes place. Furthermore, impaired Aβ-degradation in presence of capsaicinoids is dependent on the insulin-degrading-enzyme, one of the major Aβ-degrading-enzymes. Regarding Aβ-homeostasis, no differences were found between the major capsaicinoids, capsaicin and dihydrocapsaicin, and a mixture of naturally derived capsaicinoids; effects on Ca2+-homeostasis were ruled out. Our results show that in respect to Alzheimer's disease, besides the known positive effects of capsaicinoids, pro-amyloidogenic properties also exist, enhancing Aβ-levels, likely restricting the potential use of capsaicinoids as therapeutic substances in Alzheimer's disease.
DOI of the first publication: 10.1038/s41598-020-66009-6
Link to this record: urn:nbn:de:bsz:291--ds-323877
hdl:20.500.11880/29753
http://dx.doi.org/10.22028/D291-32387
ISSN: 2045-2322
Date of registration: 28-Sep-2020
Description of the related object: Supplementary information
Related object: https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-020-66009-6/MediaObjects/41598_2020_66009_MOESM1_ESM.docx
Faculty: M - Medizinische Fakultät
Department: M - Neurologie und Psychiatrie
Professorship: M - Prof. Dr. Tobias Hartmann
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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