Brain neurotrophic factor BDNF: new data, functions and questions

The brain-derived neurotrophic factor (BDNF) is a key modulator of neurogenesis, synaptogenesis, neuroregeneration, and cell differentiation in the nervous system. Impaired BDNF functioning is a characteristic of various neurological diseases, such as Alzheimer’s disease, multiple sclerosis, and depressive disorders. There is recent evidence that patients with COVID-19 have reduced BDNF levels in the blood plasma. Furthermore, exogenous BDNF and its mimetics have demonstrated therapeutic potential. In this review, we systematized data of the BDNF gene structure, epigenetic and microRNA-mediated regulation of its expression, transcriptional variants of BDNF, and the effects of BDNF on neuronal and oligodendroglial differentiation. Further, we point out the gaps in the current knowledge about BDNF and propose experiments that can expand such knowledge and the range of possibilities for using BDNF in biomedicine. These include determining the expression pattern of all BDNF gene transcripts at different stages of differentiation and in different cell subpopulations and studying the role of receptor-independent BDNF signaling, circadian fluctuations in BDNF levels, and their role in physiological and pathophysiological conditions. Finally, for translational medicine, evaluating the effect of BDNF mimetics (including those immobilized on three-dimensional scaffolds for tissue engineering) on neuronal and oligodendroglial differentiation of pluripotent and polypotent cells and identifying molecular regulators of BDNF transcription, including small molecules and microRNAs capable of regulating BDNF gene expression, are crucial.