About this item:

737 Views | 372 Downloads

Author Notes:

E-mail: kye@emory.edu

Conceived and designed the experiments: KY.

Performed the experiments: SWJ XL CBC SF WT XL GX RA QC.

Analyzed the data: SWJ SF IS WT XL GX RA QC KR KY.

Wrote the paper: KY.

The authors have declared that no competing interests exist.

Subject:

Research Funding:

This work is supported by grants from National Institute of Health RO1 CA127119 to K. Ye.

The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Deoxygedunin, a Natural Product with Potent Neurotrophic Activity in Mice

Show all authors Show less authors

Journal Title:

PLoS ONE

Volume:

Volume 5, Number 7

Publisher:

Type of Work:

Article | Final Publisher PDF

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 TrkB-dependent 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.

Copyright information:

© Jang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote