Brain-derived neurotrophic factor Regulation, effects, and potential clinical relevance

Brain-derived neurotrophic factor (BDNF) is the most ubiquitous and intensively studied member of the family of neurotrophins in the CNS. The transcriptional regulation of BDNF is complex and involves both epigenetic control and transcription factors. BDNF is produced on demand in response to neuronal activity from a precursor pro-BDNF that is transported and processed via the secretory pathway. The effects of mature BDNF are mediated by the tropomyosin-related kinase B (TrkB, tyrosine kinase B) receptor, which triggers phosphorylation cascades that promote protein synthesis, axonal growth, dendritic maturation, use-dependent synaptic plasticity, and neuroprotection. In contrast, pro-BDNF binds to the common neurotrophin receptor p75(NTR) and promotes apoptosis. BDNF can also be released from microglia and may bidirectionally affect inhibitory neurotransmission in the CNS. Disturbances in epigenetic control, transport, or signaling by BDNF may contribute to a variety of neurologic and psychiatric disorders, including Alzheimer disease (AD), Huntington disease (HD), spinocerebellar ataxia type 6 (SCA6), neuropathic pain, Rett syndrome, and depression, schizophrenia, and drug addiction. There are several recent reviews on these subjects.(1-20</SUP)