Neurotrophin Signaling Pathway

Neurotrophins (NT) are a class of protein molecules produced by nerve-innervated tissues such as muscle and astrocytes that are essential for neuronal growth and survival. Neurotrophic factors usually enter the nerve terminal through receptor-mediated entry into the cell, and then reach the cell body through reverse axoplasmic transport. They promote the synthesis of related proteins in the cell body, thereby supporting the growth, development and functional integrity of neurons. Neurotrophins include nerve growth factor (NGF), brain-derived growth factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), etc. These proteins are potential drug targets for the treatment of nerve injury and other diseases. It has been found that there are two types of high-affinity and low-affinity NT receptors on nerve terminals. The high-affinity receptors are tyrosine kinase binding receptors, including TrkA, TrkB and TrkC. These receptors are expressed in human neuronal tissues and play a crucial role in the developmental physiology and function of the nervous system through the activation of neurotrophins (NTs). Various receptors exist in the form of dimers, and their activation can promote the phosphorylation of tyrosine protein kinases in the cytoplasm. The low-affinity receptor is a 75kD membrane protein called p75NTR. The diheterozygote formed by p75NTR and TrkA monomer could enhance the specific binding affinity to NGF. However, when the homodimer formed by the polymerization of two p75NTR binds to NT, it can cause the opposite effect and even lead to apoptosis. Neurotrophin/Trk signaling is regulated by connecting various intracellular signaling cascades, including MAPK pathway, PI-3 kinase pathway and PLC pathway. On the other hand, p75NTR transmits both positive and negative signals that are important for neural development and other higher level activities such as learning and memory