Fig. 5: Schematic diagram of capsaicin inhibiting Aβ generation. | Translational Psychiatry

Fig. 5: Schematic diagram of capsaicin inhibiting Aβ generation.

From: Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice

Fig. 5

APP processing includes non-amyloidogenic and amyloidogenic pathways. In the amyloidogenic pathway, Aβ is generated by the sequential cleavage of APP by β- and γ-secretases. In the non-amyloidogenic pathway, APP is cleaved by α-secretase within the Aβ domain, which precludes Aβ generation. Increased α-secretase activity competitively inhibits amyloidogenic processing of APP and decreases Aβ production. ADAM10 is the major α-secretase responsible for ectodomain shedding of APP in the brain. proADAM10 is expressed in endoplasmic reticulum and processed in Golgi where the prodomain of proADAM10 is removed and mature ADAM10 (matADAM10) is generated; then matADAM10 is transported to the plasma membrane and executes catalytic functions. Capsaicin promotes the maturation of ADAM10, thereby shifts APP processing from amyloidogenic pathway to non-amyloidogenic pathway and precludes Aβ generation.

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