The impact of capsaicinoids on APP processing in Alzheimer's disease in SH-SY5Y cells.
Sci Rep
; 10(1): 9164, 2020 06 08.
Article
em En
| MEDLINE
| ID: mdl-32514053
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-ß (Aß), the major component of senile plaques. Treatment of neuroblastoma cells with capsaicinoids (24 hours, 10 µM) resulted in enhanced Aß-production and reduced Aß-degradation, leading to increased Aß-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 ß-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 Aß-degradation in presence of capsaicinoids is dependent on the insulin-degrading-enzyme, one of the major Aß-degrading-enzymes. Regarding Aß-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 Aß-levels, likely restricting the potential use of capsaicinoids as therapeutic substances in Alzheimer's disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Capsaicina
/
Peptídeos beta-Amiloides
/
Precursor de Proteína beta-Amiloide
/
Doença de Alzheimer
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha