LINGO-1 negatively regulates TrkB phosphorylation after ocular hypertension
LINGO-1 negatively regulates TrkB phosphorylation after ocular hypertension
复制标题
高眼压后 LINGO-1 负向调节 TrkB 磷酸化
DOI：
10.1111/j.1460-9568.2010.07127.x
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发表时间：
2010-03-01
影响因子：
3.4
通讯作者：
Mi, Sha
中科院分区：
文献类型：
--
作者：
Fu, Qing-Ling;Hu, Bing;Mi, Sha
LINGO-1（一种神经元存活的中枢神经系统特异性负调节因子）的拮抗作用被证明可以促进高眼压模型中视网膜神经节细胞（RGC）的短期存活。 LINGO-1 拮抗剂与脑源性神经营养因子 (BDNF) 相结合，可以通过尚不清楚的分子机制延长神经元存活时间。为了确定 LINGO-1 和 BDNF/TrkB 受体在神经元保护中的关系，我们在此表明 LINGO-1 与 TrkB 形成受体复合物，并在高眼压损伤后负调节其在视网膜中的激活。 LINGO-1 拮抗剂抗体 1A7 或可溶性 LINGO-1 (LINGO-1-Fc) 治疗上调磷酸-TrkB 磷酸化，导致高眼压损伤后 RGC 存活。这种神经元保护作用被抗 BDNF 抗体阻断。因此，LINGO-1 拮抗作用通过调节高眼压症后的 BDNF 和 TrkB 信号通路来促进 RGC 存活。
The antagonism of LINGO-1, a CNS-specific negative regulator of neuronal survival, was shown to promote short-term survival of retinal ganglion cell (RGC) in an ocular hypertension model. LINGO-1 antagonists, combined with brain-derived neurotrophic factor (BDNF), can increase the length of neuron survival through an unclear molecular mechanism. To determine the relationship between LINGO-1 and BDNF/TrkB receptor in neuronal protection, we show here that LINGO-1 forms a receptor complex with TrkB and negatively regulates its activation in the retina after ocular hypertension injury. LINGO-1 antagonist antibody 1A7 or soluble LINGO-1 (LINGO-1-Fc) treatment upregulates phospho-TrkB phosphorylation and leads to RGC survival after high intraocular pressure injury. This neuronal protective effect was blocked by anti-BDNF antibody. LINGO-1 antagonism therefore promotes RGC survival by regulating the BDNF and TrkB signaling pathway after ocular hypertension.