Numerous
clinical trials have reported beneficial effects of the
Ginkgo biloba extract EGb761 in the prevention and therapy of cognitive disorders including
Alzheimer's disease (AD). Although neuroprotective properties of EGb761 have been consistently reported, the molecular mechanisms of EGb761 and the specific role of its major constituents, the
flavonols and terpenlactones, are largely unknown. One major
hallmark of AD is the deposition of
amyloid-beta (A beta) as
amyloid plaques in
the brain. A beta is a cleavage product of
amyloid precursor protein (APP). Certain
proteases, called
beta-secretases (
BACE), are crucial in the formation of A beta. The purpose of the present study was to investigate the efficacy of EGb761 and its
flavonol and terpenelactone fraction to modulate BACE-1
enzyme activity and
mRNA levels in vitro and in vivo. Neither EGb761 nor its fractions affected BACE-1 activity in vitro. Furthermore, also in Neuro-2a cells and
wild-type as well as
transgenic (Tg2576)
laboratory mice, no significant effect of EGb761 on BACE-1
enzyme activity and
mRNA levels were observed. Current findings suggest that BACE-1 may not be a major molecular target of EGb761 and its
flavonol and terpenelactone fraction.
