Decrease in the Generation of Amyloid-ß Due to Salvianolic Acid B by Modulating BACE1 Activity.
Curr Alzheimer Res
; 14(11): 1229-1237, 2017.
Article
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| MEDLINE
| ID: mdl-28413985
ABSTRACT
OBJECTIVE:
Generation and accumulation of the amyloid-ß (Aß) peptide after proteolytic processing of the full length amyloid precursor protein (FL-APP) by ß-secretase (ß-site APP cleaving enzyme or BACE1) and γ-secretase are the main causal factors of Alzheimer's disease (AD). Thus, inhibition of BACE1, a rate-limiting enzyme in the production of Aß, is an attractive therapeutic approach for the treatment of AD. Recent studies suggest that salvianolic acid B (Sal B) is isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal medicine commonly used for the treatment of cardiovascular, cerebrovascular and liver diseases in China.METHOD:
In this study, we discovered that Sal B acted as a BACE1 modulator and reduced the level of secreted Aß in two different Swedish APP (SwedAPP) mutant cell lines. Using N2a-mouse and H4- human neuroglioma cell lines expressing SwedAPP, it was demonstrated that Sal B significantly and dose-dependently decreased the generation of extracellular Aß, soluble APPß (by-product of APP cleaved by BACE1), and intracellular C-terminal fragment ß from APP without influencing α-secretase and γ-secretase activity and the levels of FL-APP. In addition, using protein-docking, we determined the potential conformation of Sal B on BACE1 docking and revealed the interactions of Sal B with the BACE1 catalytic center.RESULTS:
The docking provides a feasible explanation for the experimental results, especially in terms of the molecular basis of Sal B's action. Our results indicate that Sal B is a BACE1 inhibitor and, as such, is a promising candidate for the treatment of AD.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Medicinas Tradicionales:
Medicinas_tradicionales_de_asia
/
Medicina_china
Asunto principal:
Benzofuranos
/
Péptidos beta-Amiloides
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Fármacos Neuroprotectores
/
Secretasas de la Proteína Precursora del Amiloide
Idioma:
En
Revista:
Curr Alzheimer Res
Año:
2017
Tipo del documento:
Article