Core of basic research: Clarifies the molecular mechanism by which the neurotrophin (NTF) family regulates neuronal survival, differentiation, synaptic plasticity, and injury repair. NTFs include NGF (nerve growth factor), BDNF (brain-derived neurotrophic factor), NT-3, and NT-4, exerting effects via binding to tyrosine kinase receptors (Trk) on neurons: NGF binds TrkA, BDNF/NT-4 bind TrkB, and NT-3 binds TrkC. Receptor dimerization activates tyrosine kinase activity, initiating three core signal pathways: PI3K-Akt inhibits neuronal apoptosis and promotes survival; Ras-MAPK promotes neuronal differentiation and synaptic plasticity; PLC-γ regulates calcium signals and participates in neurotransmitter release. Additionally, NTFs can bind p75NTR receptors to mediate neuronal apoptosis in the absence of Trk receptors. Research focuses on the retrograde transport of NTFs (from synaptic terminals to neuronal soma), internalization and signal regulation of Trk receptors, pathway associations with neural development (nerve fiber projection), neural injury repair (e.g., spinal cord injury), and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, reduced BDNF expression).
Core key proteins: Neurotrophins (NGF, BDNF, NT-3, NT-4), TrkA/TrkB/TrkC (tyrosine kinase receptors), p75NTR (low-affinity neurotrophin receptor), PI3K/Akt (survival signaling pathway), Ras/Raf/MEK/ERK (MAPK pathway for differentiation), PLC-γ (phospholipase C-γ), IP3R (endoplasmic reticulum calcium channel), CaMKII (calmodulin-dependent kinase II), BAD (apoptosis-related protein inhibited by Akt phosphorylation), CREB (transcription factor regulating synaptic plasticity genes), neurons, glial cells.