Neurotrophin Signaling Pathway

1. Neurotrophin Signaling Pathway Neurotrophins are a family of proteins that play an essential role in the survival, development and function of neurons. They significantly regulate axonal and dendritic growth and guidance, synaptic structure and connections, neurotransmitter release, long-term potentiation (LTP) and synaptic plasticity. Neurotrophins prevent the associated neurons from initiating programmed cell death, which allows the neurons to survive. They also induce the differentiation of progenitor cells to form neurons. During the neurogenesis, neurotrophins are chemicals that help to stimulate and control this process. The alterations of neurotrophin levels show various effects on a wide series of phenomena, including myelination, regeneration, pain, aggression, depression and substance abuse. Nevertheless, neurotrophins are not necessary for development of neuronal circuits since they are not found in Drosophila and C.elegans. Neurotrophins are initially synthesized as precursors or proneurotrophins which are cleaved to produce the mature proteins. Pro-neurotrophins are cleaved intracellularly by FURIN, an endopeptidase with specificity for the consensus sequence Arg-X-Lys/Arg-Arg, or by pro-convertases at a highly conserved dibasic amino-acid cleavage site to release carboxy-terminal mature proteins. All mature proteins are about 12 kDa in size, forming the stable and non-covalent dimers.