Brain-derived neurotrophic factor (BDNF) is a protein that plays a critical role in the development, maintenance, and function of the nervous system. It is one of the most well-studied members of the neurotrophin family, which also includes nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). BDNF is essential for the survival, growth, and differentiation of neurons during development, and it continues to support neuronal health and plasticity throughout adulthood.

BDNF is synthesized as a precursor protein, proBDNF, which is then cleaved to produce mature BDNF. Both forms have distinct roles: proBDNF is involved in apoptosis and synaptic pruning, while mature BDNF promotes neuronal survival and synaptic strengthening. BDNF exerts its effects primarily through binding to the TrkB receptor, a receptor tyrosine kinase, which activates several intracellular signaling pathways that influence neuronal growth and plasticity. Additionally, BDNF can bind to the p75 neurotrophin receptor, which can mediate different cellular responses.

In the brain, BDNF is widely expressed, with particularly high levels in the hippocampus, cortex, and basal forebrain—regions involved in learning, memory, and higher cognitive functions. BDNF is crucial for long-term potentiation (LTP), a process underlying synaptic plasticity and memory formation. It enhances synaptic transmission and facilitates the growth of dendritic spines, which are small protrusions on neurons that form synapses with other neurons.

Beyond its role in the central nervous system, BDNF is also found in peripheral tissues and is involved in energy metabolism, cardiovascular function, and the regulation of mood. It has been implicated in various neurological and psychiatric disorders. For instance, reduced BDNF levels have been associated with depression, schizophrenia, Alzheimer’s disease, and Huntington’s disease. Conversely, exercise and certain antidepressants have been shown to increase BDNF levels, which may contribute to their therapeutic effects.

Research into BDNF continues to expand, with studies exploring its potential as a biomarker for disease and a target for therapeutic interventions. Understanding BDNF’s multifaceted roles in the nervous system and beyond is crucial for developing strategies to treat neurodegenerative diseases, mental health disorders, and other conditions linked to impaired neurotrophic support.