Department of Anesthesiology, College of Medicine, Mayo Clinic, 200 First Street SW, Joseph 4W-184F, Rochester, Minnesota 55905, USA.
Muscle Nerve. 2012 Feb;45(2):274-6. doi: 10.1002/mus.22295.
Neurotrophin signaling at the neuromuscular junction modulates cholinergic transmission and enhances neuromuscular transmission via the tropomyosin-related kinase receptor subtype B (TrkB).A novel flavonoid, 7,8-dihydroxyflavone (7,8-DHF), selectively activates TrkB receptors. Using TrkB(F616A) mice that are susceptible to specific inhibition of TrkB activity by 1NMPP1, we show that neuromuscular transmission is enhanced by 7,8-DHF (∽32%) via activation of TrkB in diaphragm muscle. The small molecule 7,8-DHF may constitute a novel therapy to improve neuromuscular function.
神经营养因子信号在神经肌肉接头处调节胆碱能传递，并通过原肌球蛋白相关激酶受体亚型 B (TrkB)增强神经肌肉传递。一种新型黄酮类化合物，7,8-二羟基黄酮（7,8-DHF），选择性激活 TrkB 受体。使用易受 1NMPP1 特异性抑制 TrkB 活性影响的 TrkB(F616A) 小鼠，我们表明 7,8-DHF 通过激活膈肌中的 TrkB 将神经肌肉传递增强约 32%。小分子 7,8-DHF 可能构成改善神经肌肉功能的新疗法。
