Neurotrophin Signaling
Growth factor signaling promoting neuronal survival, differentiation, and plasticity.
Overview
Neurotrophins (NGF, BDNF, NT-3, NT-4) bind Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) with specificity, activating RAS-MAPK (differentiation), PI3K-AKT (survival), and PLCγ-PKC (synaptic plasticity) pathways. All neurotrophins also bind p75NTR, which can promote survival (with Trk) or apoptosis (without Trk). Pro-neurotrophins preferentially bind p75NTR-sortilin to induce apoptosis.
Cellular Location
Neuronal cell bodies, axon terminals, dendrites
Clinical Significance
BDNF-TrkB is essential for memory and synaptic plasticity; reduced BDNF in depression; NGF for diabetic neuropathy trials; p75NTR in neurodegeneration; exercise increases BDNF.
Key Molecules
Key Enzymes
Related Pathways
MAPK/ERK Pathway
RAS–RAF–MEK–ERK cascade transducing growth factor signals to the nucleus.
PI3K/AKT/mTOR Pathway
Regulates cell survival, growth, and metabolism via phosphoinositide signaling.
Intrinsic Apoptosis (Mitochondrial)
Cell death triggered by internal stress via mitochondrial cytochrome c release.
Long-Term Potentiation / Depression (LTP/LTD)
Activity-dependent strengthening or weakening of synaptic connections.