Novel Agonist Monoclonal Antibodies Activate TrkB Receptors and Demonstrate Potent Neurotrophic Activities
作者： Ming D Qian , Jie Zhang , Xiang-Yang Tan , Andrew Wood , Davinder Gill
DOI: 10.1523/JNEUROSCI.1118-06.2006
关键词: Monoclonal antibody 、 Cell signaling 、 Neurotrophic factors 、 Neurotrophin 、 Cell biology 、 Neuroscience 、 Neurite 、 Biology 、 Tropomyosin receptor kinase B 、 Receptor 、 Tropomyosin receptor kinase A
摘要: Tyrosine kinase receptor B (TrkB) mediates neurotrophic effects of brain-derived factor (BDNF) to increase neuronal survival, differentiation, synaptic plasticity, and neurogenesis. The therapeutic potential TrkB activation using BDNF has been demonstrated well in several preclinical models CNS diseases, validating as a promising drug target. Therefore, we aimed develop TrkB-specific agonists by monoclonal antibody approach. After generation hybridoma clones assessment their binding functional activity, identified five mouse antibodies that show highly selective induce robust signaling. Epitope mapping studies competition analysis showed each the recognizes unique site on TrkB, some which are distinct from docking sites. These behave true based ability both activate proximal secondary signaling molecules downstream receptors promote survival neurite outgrowth. affinities efficacy these comparable those BDNF, whereas they do not bind p75 low-affinity neurotrophin at all. could represent novel reagents explore pathophysiological roles its utility treating disorders.
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