Ginkgo Biloba extract modulates proteasomal activity and reduces polyglutamine aggregation in vitro and in vivo

The Ginkgo biloba leaf extract EGb 761 has a wide range of neuroprotective activities and has been proposed as a potential neuroprotectant for several neurodegenerative disorders. Our present study describes a novel modulatory effect of EGb 761 in the maintenance of protein homeostasis in cell culture and C. elegans models of polyglutamine protein aggregation of mutated huntingtin (mhtt). Analyzing proteasomal activity, which is reduced in mhtt expressing cells, we find that EGb 761 treatment leads to an increase of activity independently of the extent of mhtt aggregation. In addition, EGb 761 treatment is shown (i) to reduce the size of mhtt aggregates and (ii) to increase the soluble cytosolic mhtt fraction. Strengthening these observations, we find that EGb 761 alleviates motility defects in C. elegans bearing polyglutamine aggregates and reduces their aggregation tendency. These findings suggest that EGb 761 treatment can have modulatory properties on mhtt aggregation in vitro and in vivo, presumably by enhancing proteasomal activity.