Drug Targets in Neurotrophin Signaling in the Central and Peripheral Nervous System

Abstract

Neurotrophins are a family of proteins that play an important role in the regulation of the growth, survival, and differentiation of neurons in the central and peripheral nervous system. Neurotrophins were earlier characterized by their role in early development, growth, maintenance, and the plasticity of the nervous system during development, but recent findings also indicate their complex role during normal physiology in both neuronal and non-neuronal tissues. Therefore, it is important to recognize a deficiency in the expression of neurotrophins, a major factor driving the debilitating features of several neurologic and psychiatric diseases/disorders. On the other hand, overexpression of neurotrophins is well known to play a critical role in pathogenesis of chronic pain and afferent sensitization, underlying conditions such as lower urinary tract symptoms (LUTS)/disorders and osteoarthritis. The existence of a redundant receptor system of high-and low-affinity receptors accounts for the diverse, often antagonistic, effects of neurotrophins in neurons and non-neuronal tissues in a spatial and temporal manner. In addition, studies looking at bladder dysfunction because of conditions such as spinal cord injury and diabetes mellitus have found alterations in the levels of these neurotrophins in the bladder, as well as in sensory afferent neurons, which further opens a new avenue for therapeutic targets. In this review, we will discuss the characteristics and roles of key neurotrophins and their involvement in the central and periphery nervous system in both normal and diseased conditions.

Correlation of Artemin and GFRα3 With Osteoarthritis Pain: Early Evidence From Naturally Occurring Osteoarthritis-Associated Chronic Pain in Dogs

“…OA patients experience chronic pain, however, the molecular basis for chronic pain in these patients is still largely unknown (Eitner et al, 2017). Although it has recently been revealed that neurotrophic factors play an important role in pain transduction by activating the receptors present on the DRG sensory neurons in mice (Orozco et al, 2001;Elitt et al, 2006;Malin et al, 2006;Kashyap et al, 2018;Nencini et al, 2018), it is currently unknown whether artemin, an endogenous neurotrophic factor, and its receptor, GFRα3, play an important role in pain hypersensitivity in OA patients. Here, we combined molecular and immunological methods to explore the association of artemin and GFRα3 with OA-associated pain in dogs with OA.…”

Induction of Neuronal Differentiation of Murine N2a Cells by Two Polyphenols Present in the Mediterranean Diet Mimicking Neurotrophins Activities: Resveratrol and Apigenin

“…Promoting neurogenesis could be a means of preventing these diseases. In this context, neuropeptides produced by the brain via endothelial cells and astrocytes form a family of molecules called neurotrophins, with cytoprotective and differentiating activities [ 65 ]. However, to exert their cytoprotective effects, these molecules must be injected intracerebrally near the lesions [ 66 ].…”

Utilisation des psychédéliques en psychiatrie : lien avec les neurotrophines

“…La découverte nobélisée des neurotrophines a initialement été effectuée en relation avec leur fonction dans la maturation et le développement des circuits neuronaux (Castrén, 2014). Plus récemment, des études ont mis en évidence leur rôle chez l'adulte, soulignant leur importance pour la compréhension des troubles psychiatriques (Kashyap et al, 2018). Cette famille de petites protéines sécrétées comprend le nerve growth factor (NGF), les neurotrophines 3 (NT-3) et 4 (NT-4), et le brain-derived neurotrophic factor (BDNF) qui partagent environ 50 % d'homologie de séquence (Kashyap et al, 2018).…”

“…Plus récemment, des études ont mis en évidence leur rôle chez l'adulte, soulignant leur importance pour la compréhension des troubles psychiatriques (Kashyap et al, 2018). Cette famille de petites protéines sécrétées comprend le nerve growth factor (NGF), les neurotrophines 3 (NT-3) et 4 (NT-4), et le brain-derived neurotrophic factor (BDNF) qui partagent environ 50 % d'homologie de séquence (Kashyap et al, 2018). Les neurotrophines sont synthétisées sous la forme de protéine précurseur avec un prodomaine en N-terminal.…”

“…Les neurotrophines sont synthétisées sous la forme de protéine précurseur avec un prodomaine en N-terminal. Leur clivage aboutit à des neurotrophines matures (Kashyap et al, 2018), qui se lient à l'un et/ou l'autre des trois récepteurs TrK (tropomyosine-related kinase) : NGF à TrKA, BDNF et NT-4 à TrKB, et NT-3 à TrKC (Park & Poo, 2013). Les proneurotrophines, quant à elles, vont préférentiellement se fixer à p75NTR.…”