Inhibition of Amyloid-β Aggregation and Caspase-3 Activation by the Ginkgo biloba Extract EGb761

Authors

Yuan Luo, University of Southern MississippiFollow
Julie V. Smith, University of Southern MississippiFollow
Vijaykumar Paramasivam, University of Southern MississippiFollow
Adam Burdick, University of Southern MississippiFollow
Kenneth J. Curry, University of Southern MississippiFollow
Justin P. Buford, University of Southern MississippiFollow
Ikhlas Khan, University of MississippiFollow
William J. Netzer, The Rockefeller University
Huaxi Xu, Xiamen UniversityFollow
Peter Butko, University of Southern MississippiFollow

Document Type

Article

Publication Date

9-2002

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, has been used in clinical trials for its beneficial effects on brain functions, particularly in connection with age-related dementias and Alzheimer's disease (AD). Substantial experimental evidence indicates that EGb761 protects against neuronal damage from a variety of insults, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an AD-associated double mutation, we report that EGb761 inhibits formation of amyloid-β (Aβ) fibrils, which are the diagnostic, and possibly causative, feature of AD. The decreased Aβ fibrillogenesis in the presence of EGb761 was observed both in the conditioned medium of this Aβ-secreting cell line and in solution in vitro. In the cells, EGb761 significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of caspase 3, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that (i) neuronal damage in AD might be due to two factors: a direct Aβ toxicity and the apoptosis initiated by the mitochondria; and (ii) multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of Aβ aggregation, underlie the neuroprotective effects of EGb761.

Comments

Originally published in:

PNAS September 17, 2002 vol. 99 no. 19 12197-12202

http://www.pnas.org/content/99/19/12197.abstract

For more information, visit Dr. Curry's SelectedWorks page.

Publication Title

Proceedings of the National Academy of Sciences of the Unites States of America

Volume

99

Issue

19

First Page

12197

Last Page

12202

Recommended Citation

Luo, Y., Smith, J. V., Paramasivam, V., Burdick, A., Curry, K. J., Buford, J. P., Khan, I., Netzer, W. J., Xu, H., Butko, P. (2002). Inhibition of Amyloid-β Aggregation and Caspase-3 Activation by the Ginkgo biloba Extract EGb761. Proceedings of the National Academy of Sciences of the Unites States of America, 99(19), 12197-12202.
Available at: https://aquila.usm.edu/fac_pubs/2