Deoxygedunin, a natural product with potent neurotrophic activity in mice
Jang, Sung-Wuk (Emory University. School of Medicine. Department of Pathology and Laboratory Medicine)
Liu, Xia (Emory University. School of Medicine. Department of Pathology and Laboratory Medicine)
Chan, Chi Bun (Emory University. School of Medicine. Department of Pathology and Laboratory Medicine)
France, Stefan A. (Georgia Institute of Technology. School of Chemistry and Biochemistry)
Sayeed, Iqbal (Emory University. School of Medicine. Department of Emergency Medicine)
Tang, Wenxue (Emory University. School of Medicine. Department of Otolaryngology and Cell Biology)
Lin, Xi (Emory University. School of Medicine. Department of Otolaryngology and Cell Biology)
Xiao, Ge (Centers for Disease Control and Prevention (U.S.))
Andero Galí, Raül (Universitat Autònoma de Barcelona. Institut de Neurociències)
Chang, Qiang (University of Wisconsin-Madison. Department of Genetics and Neurology)
Ressler, Kerry J. (Emory University. School of Medicine. Department of Psychiatry and Behavioral Science)
Ye, Keqiang (Emory University. Department of Pathology and Laboratory Medicine)

Date:	2010
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 2/2 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Neurotrophic activity ; Activitat neurotròfica ; Deoxygedunin
Published in:	PloS one, Vol. 5 Issue 7 (July 2010) , p. e11528, ISSN 1932-6203

DOI: 10.1371/journal.pone.0011528.g001
DOI: 10.1371/journal.pone.0011528
PMID: 20644624

15 p, 1.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles