Brain neurotrophic factor BDNF: new data, functions and questions

Abstract

Brain-derived neurotrophic factor BDNF is one of the key modulators of neurogenesis, synaptogenesis, neuroregeneration and cell differentiation in the nervous system (NS). Impaired functioning of BDNF is a characteristic of many neurological diseases, such as Alzheimer's disease, multiple sclerosis, depressive disorders and others. There is also recent evidence that patients with COVID-19 have reduced BDNF levels in the blood plasma.At the same time, exogenous BDNF or its mimetics have demonstrated therapeutic potential. In this review, we systematized data on the structure of theBDNFgene, epigenetic and microRNA-mediated regulation of its expression, transcriptional variants ofBDNF,and effect of BDNF on neuronal and oligodendroglial differentiation.We also point out the gaps in the current knowledge about BDNF,and propose experiments that can expand such knowledge and, subsequently, the range of possibilities for using BDNF in biomedicine.These include determining the expression pattern of allBDNFgene transcripts at different stages of differentiation and in different cell subpopulations, 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, it is of practical interest to assess 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, as well as to identify molecular regulators ofBDNFtranscription including small molecules and microRNAs capable of regulatingBDNFgene expression.