BDNF

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that supports neuronal survival, development, and synaptic plasticity. It is abundant in the mammalian brain, with high levels in the hippocampus, cortex, and basal forebrain, and is also produced by some glial cells. BDNF is synthesized as a larger precursor, preproBDNF, which is processed to proBDNF and then to mature BDNF. Intracellular and extracellular proteolytic processing by convertases such as furin and plasmin generate mature BDNF, which is the form most commonly associated with synaptic potentiation.

BDNF signals through two main receptors with distinct effects. Mature BDNF binds to the TrkB receptor (NTRK2), activating intracellular pathways that promote neuronal survival, growth, and long-term potentiation. ProBDNF, in contrast, preferentially engages the p75 neurotrophin receptor (p75NTR) and, with the co-receptor sortilin, can promote apoptosis or long-term depression. Thus, proBDNF and mature BDNF can have opposing actions depending on the receptor context.

BDNF expression is activity-dependent and regulated by calcium signaling and CREB-mediated transcription. Physiological stimuli such as learning, physical exercise, and environmental enrichment increase BDNF, while stress can reduce it. A common genetic variant, Val66Met, impairs activity-dependent secretion and is associated with altered cognition and mood regulation.

In health and disease, BDNF plays a role in mood disorders, neurodegenerative diseases, and recovery after brain injury. Therapeutic strategies aim to enhance BDNF signaling or mimic its effects, though delivery and specificity remain challenges. Peripheral BDNF levels are studied as potential biomarkers but do not consistently reflect central BDNF activity.