Nerve growth factor synthesis sites

Davies, A.M., Bandtiow, C., Heumann, R., Korsching, S., Rohrer, H. and Thoenen, H, (1987) Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature 326 353-357. 

The hereditary absence of phenylalanine hydroxylase, which is found principally in the liver, is the cause of the biochemical defect phenylketonuria (Chapter 25, Section B).430 4308 Especially important in the metabolism of the brain are tyrosine hydroxylase, which converts tyrosine to 3,4-dihydroxyphenylalanine, the rate-limiting step in biosynthesis of the catecholamines (Chapter 25), and tryptophan hydroxylase, which catalyzes formation of 5-hydroxytryptophan, the first step in synthesis of the neurotransmitter 5-hydroxytryptamine (Chapter 25). All three of the pterin-dependent hydroxylases are under complex regulatory control.431 432 For example, tyrosine hydroxylase is acted on by at least four kinases with phosphorylation occurring at several sites.431 433 4338 The kinases are responsive to nerve growth factor and epidermal growth factor,434 cAMP,435 Ca2+ + calmodulin, and Ca2+ + phospholipid (protein kinase C).436 The hydroxylase is inhibited by its endproducts, the catecholamines,435 and its activity is also affected by the availability of tetrahydrobiopterin.436... 

During the development of the vertebrate nervous system most, if not all, neuronal populations undergo a period of programmed cell death. During this period neurons depend on the availability of epigenetic factors for their survival (Barde, 1989). Nerve growth factor (NGF) was the first described neurotrophic factor that was able to support the survival of subpopulations of neurons both in vivo and in vitro (see Levi-Montalcini, 1987 for review). However, NGF does not support all neuronal populations, indicating that other neurotrophic factors must also exist. The purification and characterisation of brain-derived neurotrophic factor (BDNF), and its similarities to NGF, have led to the discovery of a family of neurotrophic factors now known as the neurotrophins. This review will attempt to cover what is known about the BDNF protein, its site of synthesis and its mechanism of action. 

---