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|Title:||The impact of capsaicinoids on APP processing in Alzheimer's disease in SH-SY5Y cells|
|Author(s):||Grimm, Marcus O.W.|
Lauer, Anna A.
Haupenthal, Viola J.
Niemeyer, Barbara A.
Grimm, Heike S.
|Year of Publication:||2020|
|Free key words:||Biochemistry|
|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|
|Date of registration:||28-Sep-2020|
|Description of the related object:||Supplementary information|
|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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