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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
  • Yuan Luo, University of Southern Mississippi
  • Julie V. Smith, University of Southern Mississippi
  • Vijaykumar Paramasivam, University of Southern Mississippi
  • Adam Burdick, University of Southern Mississippi
  • Kenneth J. Curry, University of Southern Mississippi
  • Justin P. Buford, University of Southern Mississippi
  • Ikhlas Khan, University of Mississippi
  • William J. Netzer, The Rockefeller University
  • Huaxi Xu, Xiamen University
  • Peter Butko, University of Southern Mississippi
Document Type
Article
Publication Date
7-1-2002
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.
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Originally published in:

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

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

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Citation Information
Yuan Luo, Julie V. Smith, Vijaykumar Paramasivam, Adam Burdick, et al.. "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 Vol. 99 Iss. 19 (2002) p. 12197 - 12202
Available at: http://works.bepress.com/kenneth_curry/5/