Deoxygedunin, a natural product with potent neurotrophic activity in mice.

Deoxygedunin, a natural product with potent neurotrophic activity in mice.
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DOI:
10.1371/journal.pone.0011528
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发表时间:
2010-07-13
期刊:
影响因子:
3.7
通讯作者:
Ye K
Ye K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jang SW;Liu X;Chan CB;France SA;Sayeed I;Tang W;Lin X;Xiao G;Andero R;Chang Q;Ressler KJ;Ye K

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Gedunin是印度楝属植物中的一类天然产物,具有多种生物活性。在这里,我们报告发现deoxygedunin,它激活小鼠TrkB受体及其下游信号级联。脱氧gedunin可口服,并以BDNF非依赖性方式激活小鼠脑中的TrkB。引人注目的是,它可以防止BDNF −/−幼崽的前庭神经节退化。此外,deoxygedunin以TrkB依赖的方式有力地保护大鼠神经元免于细胞死亡。此外,向小鼠施用脱氧盖杜宁显示出有效的神经保护、抗抑郁和学习增强作用,所有这些都是由TrkB受体介导的。因此,deoxygedunin通过激活TrkB来模拟BDNF的生物活性,为治疗各种神经系统疾病提供了强有力的治疗工具。
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.
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