BDNF and TrkB

Brain-derived neurotrophic factor (BDNF, abrineurin) is one of neurotrophin proteins. BDNF binds to and activates tropomyosin receptor kinase B, also known as tyrosine receptor kinase B (TrkB, NTRK2) on neurons of CNS and PNS, promoting neurogenesis and neuroplasticity, and modulating the activity of various neurotransmitter receptors. BDNF and other neurotrophins bind also to p75 neurotrophin receptor (p75NTR, LNGFR), which may trigger apoptosis in the absence of Trk receptors. Dysregulation of the BDNF/TrkB system has been implicated in neurological, neurodegenerative, and psychiatric conditions, including AD, PD, HD, ALS, and ischemic stroke, but also in cancer. Some antidepressants and psychedelics bind to TrkB (Moliner et al., 2023).

Trk inhibitors have been labelled with radioactive labels for Trk imaging. [18F]TRACK has shown good selectivity towards TrkB and TrkC, fast reversible binding kinetics, and favourable dosimetry (Bernard-Gauthier et al., 2018; Bailey et al., 2019; Thiel et al., 2023).


Literature

Ateaque S, Merkouris S, Barde YA. Neurotrophin signalling in the human nervous system. Front Mol Neurosci. 2023; 16: 1225373. doi: 10.3389/fnmol.2023.1225373.

Meeker R, Williams K. Dynamic nature of the p75 neurotrophin receptor in response to injury and disease. J Neuroimmune Pharmacol. 2014; 9(5): 615-628. doi: 10.1007/s11481-014-9566-9.

Numakawa T, Odaka H, Adachi N. Actions of brain-derived neurotrophin factor in the neurogenesis and neuronal function, and its involvement in the pathophysiology of brain diseases. Int J Mol Sci. 2018; 19(11): 3650. doi: 10.3390/ijms19113650.



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Updated at: 2023-10-30
Created at: 2023-10-30
Written by: Vesa Oikonen