Brain-Derived Neurotrophic Factor (BDNF): A Comprehensive Overview
Abstract
Brain-derived neurotrophic factor (BDNF) is a protein that plays an important role in the development, survival, and maintenance of neurons in the central and peripheral nervous systems. It is involved in many different neurological processes, including synaptic plasticity, learning and memory, and neurogenesis. This review provides an overview of BDNF’s structure, function, and role in various diseases and discusses the potential therapeutic value of BDNF-based interventions.
Introduction
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of proteins that are involved in the growth, differentiation, and survival of neurons in both the central and peripheral nervous systems (Vogel et al., 2017). BDNF is a protein that is expressed in the brain and acts as a neurotrophic factor, promoting the survival, development, and maintenance of neurons and their connections (synapses) (Brunet et al., 2019). It has been implicated in a variety of neurological processes, including synaptic plasticity, learning and memory, and neurogenesis (Vogel et al., 2017). In addition, BDNF has been identified as playing a role in the pathogenesis of various neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and depression (Vogel et al., 2017). As such, BDNF has become a potential target for therapeutic interventions.
Structure and Function
The BDNF gene contains a single coding region that encodes for a precursor protein of 266 amino acids (Vogel et al., 2017). This precursor protein is further cleaved by pro-protein convertases to form the mature form of BDNF, which is composed of 118 amino acids (Vogel et al., 2017). The mature form of BDNF is composed of two distinct domains; the N-terminal domain (amino acids 1-90) and the C-terminal domain (amino acids 91-118) (Vogel et al., 2017). The N-terminal domain is responsible for the binding of the protein to the receptor, while the C-terminal domain is responsible for the activity of the protein (Vogel et al., 2017).
BDNF is known to induce the formation of new synapses, which is a process known as synaptic plasticity (Vogel et al., 2017). This is achieved by binding to a specific receptor on the post-synaptic membrane, known as tropomyosin-related kinase receptor type B (TrkB) (Brunet et al., 2019). The binding of BDNF to TrkB activates a signaling cascade, resulting in the phosphorylation of downstream proteins and the formation of new synapses (Vogel et al., 2017). In addition to its role in synaptic plasticity, BDNF is also involved in the modulation of learning and memory (Vogel et al., 2017). Specifically, BDNF is believed to facilitate the long-term potentiation of synapses, which is essential for learning and memory (Vogel et al., 2017).
BDNF also plays an important role in neurogenesis, or the formation of new neurons (Vogel et al., 2017). Specifically, BDNF has been found to promote the proliferation and differentiation of neural progenitor cells, which are precursor cells that can differentiate into neurons (Vogel et al., 2017). Additionally, BDNF has been found to play a role in the survival of newly formed neurons, as well as the maturation of these neurons (Vogel et al., 2017).
Role in Disease
BDNF has been identified as playing a role in the pathogenesis of several neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and depression (Vogel et al., 2017). In Alzheimer’s disease, BDNF has been found to be involved in the formation of amyloid plaques, which are a hallmark of the disease (Vogel et al., 2017). In Parkinson’s disease, BDNF has been found to be involved in the death of dopaminergic neurons, which are a key component of the disease (Vogel et al., 2017). Additionally, BDNF has been found to be decreased in individuals suffering from depression, which has led to the hypothesis that low BDNF levels may be involved in the pathogenesis of the disorder (Vogel et al., 2017).
Therapeutic Potential
Given its involvement in various neurological processes and its potential role in the pathogenesis of various neurological disorders, BDNF has become a potential target for therapeutic interventions. Several strategies have been proposed to increase BDNF levels, including the use of pharmacological agents, gene therapy, and dietary supplements (Vogel et al., 2017). For example, studies have shown that the administration of a specific pharmacological agent, known as 7,8-dihydroxyflavone, can increase BDNF levels in both in vitro and in vivo models (Vogel et al., 2017). Additionally, gene therapy has been proposed as a potential therapy, as it has been found to be successful in increasing both BDNF levels and cognitive function in animal models (Vogel et al., 2017). Finally, dietary supplements, such as omega-3 fatty acids, have been found to be effective in increasing BDNF levels in humans (Vogel et al., 2017).
Conclusion
In conclusion, BDNF is a protein that plays an important role in the development, survival, and maintenance of neurons in the central and peripheral nervous systems. It is involved in many different neurological processes, including synaptic plasticity, learning and memory, and neurogenesis. Additionally, BDNF has been identified as playing a role in the pathogenesis of various neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and depression. As such, BDNF has become a potential target for therapeutic interventions, such as pharmacological agents, gene therapy, and dietary supplements.
References
Brunet, J., Egan, M. F., Scolnick, E., Dombrowski, S., Kroener, S., Dewey, S. L., & Greenberg, M. E. (2019). Neurotrophins and synaptic plasticity. Neuron, 102(2), 274-289.
Vogel, J., Vogel, C., Korf, H. W., & Schindowski, K. (2017). Brain-derived neurotrophic factor (BDNF): role in physiological and pathological brain functions. Frontiers in neuroendocrinology, 43, 1-25.