Regulation of neurotrophin receptor (Trk) signaling: suppressor of cytokine signaling 2 (SOCS2) is a new player

Abstract

The classic neurotrophins Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF) and Neurotrophins NT-3 and NT-4 are well known to regulate various aspects of neuronal differentiation, survival and growth. They do this by binding to their cognate receptors, members of the Tropomyosin-related kinase (Trk) receptor tyrosine kinase family, namely TrkA, TrkB, and TrkC. These receptors are then internalized and localized to different cellular compartments, where signal transduction occurs. Conversely, members of the suppressor of cytokine signaling (SOCS) family are best known as negative regulators of signaling via the JAK/STAT pathway. Some members of the family, and in particular SOCS2, have roles in the nervous system that at least partially overlap with that of neurotrophins, namely neuronal differentiation and neurite outgrowth. Recent evidence suggests that SOCS2 is a novel regulator of NGF signaling, altering TrkA cellular localization and downstream signaling to affect neurite growth but not neuronal survival. This review first discusses regulation of Trk receptor signaling, followed by the role of SOCS2 in the nervous system and finishes with a discussion of possible mechanisms by which SOCS2 may regulate TrkA function.

Exploring the potential of natural and synthetic neuroprotective steroids against neurodegenerative disorders: A literature review

“…Literature reports indicate that neuronal apoptosis induced by the neurotoxicant trimethyltin is inhibited by the EPO treatment in the primary cultured hippocampal neurons . In addition EPO promotes the transcription of the cAMP responsive element binding protein as well as the expression and the production of BDNF, (v) neuroprotective effects by several neurotrophins against oxidative stress and apoptosis‐induced neuronal cell death . The neurotrophins mainly include brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), insulin‐like growth factor‐1 (IGF‐1), glial cell derived factor neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), ciliary neurotrophic factor (CNTF) neurotrophin‐3, neurotrophin‐4.…”

“…The neurotrophins mainly include brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), insulin‐like growth factor‐1 (IGF‐1), glial cell derived factor neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), ciliary neurotrophic factor (CNTF) neurotrophin‐3, neurotrophin‐4. The neurotrophins BDNF and NGF have been extensively explored with respect to their protective effects on neuron survival in neurodegenerative conditions . BDNF and NGF protect the hippocampal progenitor cells from staurosporine‐induced apoptosis by stimulating the phosphatidylinositol‐3‐kinase/Akt pathway through tropomyosin‐related kinase Trk receptors .…”

Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine

“…NT-3-positive BM-MSC administration to the injured spinal cords facilitated axonal regeneration, promoted neuronal survival [225], and favoured remyelination and functional recovery in the demyelinated spinal cords of the studied animals [226]. NT-3 acts through tropomyosin-related kinase receptor tyrosine kinases (Trk) [227], a feature that was used for BM-MSC transduction with Trk type C (TrkC) gene overexpression [228]. TrkC-producing MSCs possessed the ability to prolong their survival after delivery, improve differentiation toward neuron-like cells, and participated in corticospinal tract regeneration in the injured areas, mainly due to the elevated concentration of NT-3.…”

Endogenous Neuroprotective Molecules and Their Mechanisms in the Central Nervous System

“…The neurotrophins BDNF and NGF have been extensively studied with respect to their positive effect on neuron survival in neurodegenerative disorders and nerve injuries of the CNS. [24][25][26] BDNF and NGF protected hippocampal progenitor cells from staurosporine-induced apoptosis by stimulating the phosphatidylinositol-3-kinase/Akt pathway through the Trk receptors.…”