The Neurotrophin Family of Neurotrophic Factors: An Overview

Abstract

The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons and have since been shown to control a number of aspects of survival, development, and function of neurons in both the central and peripheral nervous systems. Limiting quantities of neurotrophins during development control the numbers of surviving neurons to ensure a match between neurons and the requirement for a suitable density of target innervation. Biological effects of each of the four mammalian neurotrophins are mediated through activation of one or more of the three members of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases (TrkA, TrkB, and TrkC). In addition, all neurotrophins activate the p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily. Neurotrophin engagement of Trk receptors leads to activation of Ras, phosphatidylinositol 3-kinase, phospholipase C-γ1, and signaling pathways controlled through these proteins, including the mitogen-activated protein kinases. Neurotrophin availability is required into adulthood, where they control synaptic function and plasticity and sustain neuronal cell survival, morphology, and differentiation. This chapter will provide an overview of neurotrophin biology, their receptors, and signaling pathways.

Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands during development and lactation

“…Neurotrophins are growth factors primarily described in the development and survival of neural cells (Skaper 2012). The neurotrophin family is composed of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 4 (NT-4).…”

Expression of NGF, BDNF and their receptors in subcutaneous adipose tissue of lactating cows

“…In a number of murine tissues, the development and survival of sympathetic neurons depend upon the presence of target-derived neurotrophins the best characterized of which is nerve growth factor (NGF) in BAT (Nisoli et al, 1996) and WAT (Peeraully et al, 2004). In spite of their function as growth factors primarily for development and survival of neural cells (Skaper, 2012), Chaldakov et al (2010) reported that many neuropeptides, neurotrophic factors and receptors are shared by the brain and adipocytes, hence, proposing adipose tissue as a member of the diffuse neuroendocrine system.…”

The role of nerve growth factor and its receptors in tumorigenesis and cancer pain

“…Recent studies demonstrated that TrkA expression was increased during the progression of medullary thyroid carcinoma and neuroblastoma (70). domain can be phosphorylated and bind to a number of death-signalling proteins (40,41).…”

“…Unlike p75NTR which can be activated by all neurotrophin family members, TrkA is activated only by particular neurotrophins (Figure 1) (40,(42)(43)(44). Like most receptor tyrosine kinases, TrkA is activated by ligand-induced formation of non-covalently associated receptor dimers (43).…”