Key molecules in axon regeneration

Abstract

Development of adult mammal central nervous system (CNS) is closely related to loosing the ability spontaneously regenerate after injuries. On the other hand, peripheral nervous system (PNS) maintains its capability to regenerate after injuries entire lifespan. Ability to regenerate successfully is mainly determined by the balance of growth promoting and growth inhibiting factors, expressed by both neuronal and non-neuronal cells found in the injury site. Some of signaling cues involved in regeneration are expressed in adult CNS constantly, although expression of other factors occurs only in the injury site of adult mammal. Ephrins, Semaphorins, Slits and Netrins are among most important molecules involved in lack of success in regeneration of CNS. PNS neurons initiate reparation mechanisms right after development of injury, and are capable to recover functional activity even if an area of injury is more than several centimeters wide. Understanding of differences between CNS and PNS regeneration and factors involved in functional nervous system recovery are crucial for both in depth analysis of plasticity of adult mammal neural system, and for developing new treatment strategies.

Endogenous Glycoprotein GPM6a Is Involved in Neurite Outgrowth in Rat Dorsal Root Ganglion Neurons

“…After a neurotraumatic injury, a regenerative program is switched on by expressing proteins involved in neuronal development [ 13 ]. To reproduce an axonal injury condition, adult DRGs can be harvested in vivo, and then neurons may be dissociated and replaced in a dish (in vitro) [ 50 , 51 , 52 ].…”

“…As mentioned, an injury to the peripheral nerve triggers a sequence of events that cause the up- and down-regulation of specific proteins [ 13 ]. In the CNS, GPM6a was found to be an essential element for neurite outgrowth in several in vitro models [ 20 , 21 , 22 , 26 , 27 , 60 ] and for axonal elongation in primary neuron cultures using naïve [ 61 ] and GPM6a-knockout mice [ 24 ].…”

“…DRG neurons are pseudo-unipolar; they possess a single axon extending from the cell body, and then it bifurcates into a central axonal branch (to the spinal cord) and a peripheral axonal branch to their target tissues, [ 11 , 12 ]. After an injury, DRG neurons induce axon regeneration by adjusting the expression of cell adhesion molecules, neurotrophins (NTs), growth factors receptors, and cytoskeletal molecules, among others [ 13 ]. For instance, NTs, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3), along with their cognate receptors (TrKA, TrKB, and TrKC), are critical for the survival, development, and maintenance of DRG neurons [ 14 , 15 ].…”