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Merck

TrkB agonistic antibodies superior to BDNF: Utility in treating motoneuron degeneration.

Neurobiology of disease (2019-08-31)
Wei Guo, Keliang Pang, Yanbo Chen, Shudan Wang, Heng Li, Yihua Xu, Fang Han, Hongyang Yao, Hang Liu, Vanessa Lopes-Rodrigues, Dang Sun, Jingyu Shao, Jianying Shen, Yang Dou, Wen Zhang, He You, Wutian Wu, Bai Lu
RESUMEN

While Brain-derived Neurotrophic Factor (BDNF) has long been implicated in treating neurological diseases, recombinant BDNF protein has failed in multiple clinical trials. In addition to its unstable and adhesive nature, BDNF can activate p75NTR, a receptor mediating cellular functions opposite to those of TrkB. We have now identified TrkB agonistic antibodies (TrkB-agoAbs) with several properties superior to BDNF: They exhibit blood half-life of days instead of hours, diffuse centimeters in neural tissues instead millimeters, and bind and activate TrkB, but not p75NTR. In addition, TrkB-agoAbs elicit much longer TrkB activation, reduced TrkB internalization and less intracellular degradation, compared with BDNF. More importantly, some of these TrkB-agoAbs bind TrkB epitopes distinct from that by BDNF, and work cooperatively with endogenous BDNF. Unlike BDNF, the TrkB-agoAbs exhibit a half-life of days/weeks and diffused readily in nerve tissues. We tested one of TrkB-agoAbs further and showed that it enhanced motoneuron survival in the spinal-root avulsion model for motoneuron degeneration in vivo. Thus, TrkB-agoAbs are promising drug candidates for the treatment of neural injury.

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Sigma-Aldrich
Medio para gradiente de densidad OptiPrep, used for cell and subcellular organelle isolation
Sigma-Aldrich
Polyethylene glycol/ dimethyl sulfoxide solution, Hybri-Max, average mol wt 1,450, 50 % (w/v), 0.2 μm filtered, BioReagent, suitable for hybridoma