Effect of mycelial extract of Clavicorona pyxidata on the production of amyloid beta-peptide and the inhibition of endogenous beta-secretase activity in vitro

Abstract

Amyloid beta-peptide (Abeta), which is a product of the proteolytic effect of beta-secretase (BACE) on an amyloid precursor protein, is closely associated with Alzheimer's disease (AD) pathogenesis. There is sufficient evidence to suggest that a BACE inhibitor may reduce Abeta levels, thus decreasing the risk of AD. In a previous study, an extract of Clavicorona pyxidata DGUM 29005 mycelia was found to inhibit the production of a soluble beta-amyloid precursor protein (sbetaAPP), Abeta, and BACE in neuronal cell lines. We sought to determine whether this mycelial extract exerts the same effect in human rhabdomyosarcoma A-204 and rat pheochromocytoma PC-12 cells. We found that the production of Abeta decreased in a dose-dependent manner in the presence of the mycelial extract and that the concentration of Abeta never exceeded 50 microg/ml. The presence of sAPP was detected in every culture medium to which the mycelial extract had been added and its concentration remained the same, regardless of the concentration of the extract used. Endogenous beta-secretase activity in A-204 and PC-12 cellular homogenates also decreased in the presence of this extract. These cells, in culture, were not susceptible to the cytotoxic activity of the mycelial extract.