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Deoxygedunin, a natural product with potent neurotrophic activity in mice

By Ge Xiao, Sung Wuk Jang, Xia Liu, Chi Bun Chan, Stefan A. France, Iqbal Sayeed, Wenxue Tang, Xi Lin, Keqiang Ye, Raul Andero, Qiang Chang and Kerry J. Ressler

Abstract

Gedunin, a family of natural products from the Indian neem tree, possess a variety of biological activities. Here we report the discovery of deoxygedunin, which activates the mouse TrkB receptor and its downstream signaling cascades. Deoxygedunin is orally available and activates TrkB in mouse brain in a BDNF-independent way. Strikingly, it prevents the degeneration of vestibular ganglion in BDNF -/- pups. Moreover, deoxygedunin robustly protects rat neurons from cell death in a TrkBdependent manner. Further, administration of deoxygedunin into mice displays potent neuroprotective, anti-depressant and learning enhancement effects, all of which are mediated by the TrkB receptor. Hence, deoxygedunin imitates BDNF's biological activities through activating TrkB, providing a powerful therapeutic tool for treatment of various neurological diseases. © 2010 Jang et al.Link_to_subscribed_fulltex

Publisher: 'Public Library of Science (PLoS)'
Year: 2010
DOI identifier: 10.1371/journal.pone.0011528
OAI identifier: oai:hub.hku.hk:10722/225084
Provided by: HKU Scholars Hub
Journal:

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