The impact of capsaicinoids on APP processing in Alzheimer's disease in SH-SY5Y cells.

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-? (A?), the major component of senile plaques. Treatment of neuroblastoma cells with capsaicinoids (24?hours, 10?µM) resulted in enhanced A?-production and reduced A?-degradation, leading to increased A?-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 ?-secretase-activity. Additionally, ?-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 A?-degradation in presence of capsaicinoids is dependent on the insulin-degrading-enzyme, one of the major A?-degrading-enzymes. Regarding A?-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 A?-levels, likely restricting the potential use of capsaicinoids as therapeutic substances in Alzheimer's disease.

SUBMITTER: Grimm MOW 

PROVIDER: S-EPMC7280252 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature