Neurotrophin-4: Discovery, Tissue Distribution, and Biological Effects

Neurotrophin-4 (NT-4) is the least studied member of the neurotrophin family—proteins that play a key role in the development and functioning of the nervous system. The review presents current data on its discovery, structure, tissue localization, and biological functions. It has been shown that NT-4, like BDNF, interacts predominantly with the TrkB receptor but possesses a number of unique features in its mechanism of action and spectrum of physiological effects. The involvement of NT-4 in the regulation of sensory innervation, appetite control, long-term memory formation, maintenance of fertility, and motor innervation of muscles is considered. The neuroprotective properties of NT-4 in models of neurodegenerative diseases, brain injury, and stroke are summarized, as well as its possible role in the pathogenesis of psychiatric disorders, addiction, and other diseases. The therapeutic potential of NT-4 and the relevance of developing its low-molecular-weight mimetics is emphasized.