Abstract
Signal Transduction Antidepressants are clinically effective and widely used but their mechanisms of action are not fully understood. Casarotto et al. propose that several different types of antidepressants all act directly on the neuronal receptor tyrosine kinase receptor 2 (TRKB). TRKB is the receptor for brain-derived neurotrophic factor, regulates activity-dependent synaptic plasticity, and has been implicated in antidepressant actions. The authors found three different types of antidepressant bound with relatively low affinity to the transmembrane domain of TRKB. Mutation of the site impaired antidepressant action in cellular and animal studies. The authors propose that the low-affinity binding can help to explain the known slow time course of antidepressant action, which might reflect slow accumulation of the drugs in the brain to reach a dose that enhances TRKB signaling. Cell 184 , P1299 (2021).
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