TrkB transmembrane domain: bridging structural understanding with therapeutic strategy

Giray Enkavi; Mykhailo Girych; Rafael Moliner; Ilpo Vattulainen; Eero Castrén

doi:10.1016/j.tibs.2024.02.001

TrkB transmembrane domain: bridging structural understanding with therapeutic strategy

Trends Biochem Sci. 2024 Mar 2:S0968-0004(24)00037-9. doi: 10.1016/j.tibs.2024.02.001. Online ahead of print.

Authors

Giray Enkavi¹, Mykhailo Girych¹, Rafael Moliner², Ilpo Vattulainen³, Eero Castrén⁴

Affiliations

¹ Department of Physics, University of Helsinki, Helsinki, Finland.
² Neuroscience Center/HiLIFE, University of Helsinki, Helsinki, Finland.
³ Department of Physics, University of Helsinki, Helsinki, Finland. Electronic address: ilpo.vattulainen@helsinki.fi.
⁴ Neuroscience Center/HiLIFE, University of Helsinki, Helsinki, Finland. Electronic address: eero.castren@helsinki.fi.

PMID: 38433044
DOI: 10.1016/j.tibs.2024.02.001

Abstract

TrkB (neuronal receptor tyrosine kinase-2, NTRK2) is the receptor for brain-derived neurotrophic factor (BDNF) and is a critical regulator of activity-dependent neuronal plasticity. The past few years have witnessed an increasing understanding of the structure and function of TrkB, including its transmembrane domain (TMD). TrkB interacts with membrane cholesterol, which bidirectionally regulates TrkB signaling. Additionally, TrkB has recently been recognized as a binding target of antidepressant drugs. A variety of different antidepressants, including typical and rapid-acting antidepressants, as well as psychedelic compounds, act as allosteric potentiators of BDNF signaling through TrkB. This suggests that TrkB is the common target of different antidepressant compounds. Although more research is needed, current knowledge suggests that TrkB is a promising target for further drug development.

Keywords: allosteric modulators; antidepressant drugs; cholesterol; neuroplasticity; neurotrophic factors; psychedelics.

Publication types

Review