Framing anti-depressant action

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Science  02 Apr 2021:
Vol. 372, Issue 6537, pp. 44-45
DOI: 10.1126/science.372.6537.44-f

Essentially, all antidepressant drugs increase the expression and signaling of brain-derived neurotrophic factor (BDNF). These drugs act through tyrosine kinase receptor 2 (TRKB), the receptor for BDNF, to regulate neuronal plasticity. Casarotto et al. investigated the potential interactions among TRKB, cholesterol, and antidepressants. The authors found that a dimer of TRKB forms a binding pocket, where several antidepressants from different drug classes bind with a low but physiologically meaningful affinity. This low-level binding depends on membrane cholesterol to stabilize the TRKB structure in synaptic membranes and thereby promotes BDNF signaling. Such direct binding to TRKB and promotion of BDNF-mediated plasticity may therefore be a common mechanism of action for anti-depressant drugs.

Cell, 184, 1299 (2021).

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