Diverse antidepressants were recently described to bind to TrkB (tyrosine kinase B) and drive a positive allosteric modulation of endogenous BDNF (brain-derived neurotrophic factor). Although neurotrophins such as BDNF can bind to p75NTR (p75 neurotrophin receptor), their precursors are the high-affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely opposite physiological changes, TrkB and p75NTR feature a crosslike conformation dimer and carry a cholesterol-recognition amino acid consensus in the transmembrane domain. As such qualities were found to be crucial for antidepressants to bind to TrkB and drive behavioral and neuroplasticity effects, we hypothesized that their effects might also depend on p75NTR.

中文翻译：

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氟西汀和氯胺酮通过触发 p75 神经营养因子受体蛋白水解途径增强灭绝记忆和大脑可塑性


最近描述了多种抗抑郁药与 TrkB （酪氨酸激酶 B） 结合并驱动内源性 BDNF （脑源性神经营养因子） 的正变构调节。尽管 BDNF 等神经营养因子可以与 p75NTR（p75 神经营养因子受体）结合，但它们的前体是高亲和力的 p75NTR 配体。虽然 TrkB 和 p75NTR 属于能够诱导完全相反生理变化的不相关受体家族，但具有交叉样构象二聚体，并在跨膜结构域中携带胆固醇识别氨基酸共有。由于发现这些特性对于抗抑郁药与 TrkB 结合并驱动行为和神经可塑性效应至关重要，我们假设它们的作用也可能取决于 p75NTR。