The neurotrophin receptor family of RTKs include tropomyosin-related kinase (Trk) receptors TrkA, TrkB and TrkC. Their cognate ligands are NGF, BDNF and neurotrophin-3, respectively. They are associated primarily with proliferative and migration effects in neural systems. Various isoforms of neurotrophin receptors exist, including truncated forms of TrkB and TrkC, which lack catalytic domains. p75 (TNFRSF16, also known as nerve growth factor receptor) can interact with neurotrophins and their propeptides. While p75 can lead to apoptosis, it can also form a complex with Trk receptors to mediate survival signalling [5].

[¹²⁵I]NGF (human) and [¹²⁵I]BDNF (human) have been used to label the TrkA and TrkB receptor, respectively. p75 influences the binding of NGF (NGF, P01138) and neurotrophin-3 (NTF3, P20783) to TrkA. The ligand selectivity of p75 appears to be dependent on the cell type; for example, in sympathetic neurons, it binds neurotrophin-3 (NTF3, P20783) with comparable affinity to TrkC [6].

Small molecule agonists of trkB have been described, including LM22A4 [8], while ANA12 has been described as a non-competitive antagonist of BDNF binding to trkB [4]. GNF5837 is a family-selective tyrosine kinase inhibitor [1], while the tyrosine kinase activity of the TrkA receptor can be inhibited by GW441756 (pIC₅₀= 8.7, [12]) and tyrphostin AG879 [10].

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8. Massa SM, Yang T, Xie Y, Shi J, Bilgen M, Joyce JN, Nehama D, Rajadas J, Longo FM. (2010) Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J Clin Invest, 120 (5): 1774-85. [PMID:20407211]

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Francis S. Lee Weill Cornell Medicine NewYork-Presbyterian 525 East 68th Street New York NY 10065 USA Chloe J. Peach Division of Physiology, Pharmacology & Neuroscience School of Life Sciences, Centre of Membrane Proteins and Receptors (COMPARE) University of Nottingham Medical School Nottingham NG7 2UH UK