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Deoxygedunin, a natural product with potent neurotrophic activity in mice

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... Full description

Journal Title: PloS one 13 July 2010, Vol.5(7), pp.e11528
Main Author: Jang, Sung-Wuk
Other Authors: Liu, Xia , Chan, Chi Bun , France, Stefan A , Sayeed, Iqbal , Tang, Wenxue , Lin, Xi , Xiao, Ge , Andero, Raul , Chang, Qiang , Ressler, Kerry J , Ye, Keqiang
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; PMID: 20644624 Version:1 ; DOI: 10.1371/journal.pone.0011528
Link: http://pubmed.gov/20644624
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recordid: medline20644624
title: Deoxygedunin, a natural product with potent neurotrophic activity in mice
format: Article
creator:
  • Jang, Sung-Wuk
  • Liu, Xia
  • Chan, Chi Bun
  • France, Stefan A
  • Sayeed, Iqbal
  • Tang, Wenxue
  • Lin, Xi
  • Xiao, Ge
  • Andero, Raul
  • Chang, Qiang
  • Ressler, Kerry J
  • Ye, Keqiang
subjects:
  • Limonins -- Pharmacology
  • Neurons -- Drug Effects
ispartof: PloS one, 13 July 2010, Vol.5(7), pp.e11528
description: 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.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; PMID: 20644624 Version:1 ; DOI: 10.1371/journal.pone.0011528
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


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titleDeoxygedunin, a natural product with potent neurotrophic activity in mice
creatorJang, Sung-Wuk ; Liu, Xia ; Chan, Chi Bun ; France, Stefan A ; Sayeed, Iqbal ; Tang, Wenxue ; Lin, Xi ; Xiao, Ge ; Andero, Raul ; Chang, Qiang ; Ressler, Kerry J ; Ye, Keqiang
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descriptionGedunin, 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.
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abstractGedunin, 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.
doi10.1371/journal.pone.0011528
pmid20644624
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date2010-07-13