The BDNF signaling pathway is a critical molecular mechanism that regulates key functions in the central nervous system, particularly neuronal survival, differentiation, and synaptic plasticity. BDNF (Brain-Derived Neurotrophic Factor) is a protein growth factor that primarily acts by binding to two types of receptors on the cell surface, leading to distinct cellular outcomes. BDNF's effects are mediated by its binding to a high-affinity receptor and a low-affinity receptor. High-Affinity Receptor: The most important pathway for BDNF's beneficial effects involves the tropomyosin receptor kinase B. When the active form of BDNF (mature BDNF, or m-BDNF) binds to TrkB, the receptor is induced to form a dimer (two receptors join together). This dimerization triggers the activation and autophosphorylation of the intracellular tyrosine kinase domain. Phosphorylated TrkB then acts as a docking site, activating several major intracellular signaling cascades. The MAPK/ERK pathway primarily promotes neuronal differentiation and growth. The PI3K/AKT pathway is crucial for neuronal survival and inhibiting apoptosis (programmed cell death). The PLC gamma pathway is involved in synaptic plasticity and the release of intracellular calcium. Neurogenesis (formation of new neurons), Neuronal survival and growth, Enhancement of synaptic plasticity (essential for learning and memory. Axon and dendrite growth. The Low-Affinity Receptor p75NTRBDNF also binds to the p75 neurotrophin receptor, which generally mediates opposing, or less desirable, effects. The precursor form of BDNF (pro-BDNF) preferentially binds to p75NTRBDNF. This binding can activate pathways that are associated with cellular stress and death. Promotion of neuronal apoptosis (cell death). Facilitation of synaptic Long-Term Depression (LTD), which weakens synaptic connections. It can also act as a co-receptor with TrkB to fine-tune its activity.