Brain-Derived Neurotrophic Factor (BDNF)
The most abundant neurotrophin in the brain, critical for learning, memory, and synaptic plasticity. BDNF acts through TrkB receptors and is increased by exercise and reduced by chronic stress. Low BDNF is associated with depression and cognitive decline. Some peptides are investigated for BDNF-modulating effects.
Technical Context
BDNF is synthesised as a precursor (proBDNF, 32 kDa) that is cleaved to mature BDNF (14 kDa) by furin/proconvertases intracellularly or by plasmin/MMP-9 extracellularly. Crucially, proBDNF and mature BDNF have opposing effects: proBDNF binds p75NTR → promotes apoptosis and LTD (synaptic weakening); mature BDNF binds TrkB → promotes survival, LTP (synaptic strengthening), and neuroplasticity. The Val66Met polymorphism (rs6265) affects BDNF secretion — Met carriers have impaired activity-dependent BDNF secretion, associated with reduced hippocampal volume, impaired episodic memory, and increased susceptibility to mood disorders. BDNF levels in blood (serum/plasma): low BDNF is associated with depression, Alzheimer's disease, and obesity (BDNF also regulates appetite and energy homeostasis via hypothalamic TrkB receptors). Exercise robustly increases BDNF — one proposed mechanism for the cognitive benefits of physical activity. Trofinetide's mechanism (GPE tripeptide from IGF-1) does not directly involve BDNF but addresses overlapping neuroprotective pathways.