Screening The Binding Peptides Of NEP1-35 And NgR To Improve The Regeneration Of Central Nervous System

The inability of adult mammalian central nervous system (CNS) axons to regenerate can result in the loss of some important functions permanently, while in the peripheral nervous system (PNS), not only axons can regenerate but lost functions resume generally. Interestingly, axonal regeneration will be observed if embryonic peripheral nervous tissue be transplanted to the region of injury, which indicates that the lack of regeneration of CNS is partly attributed to growth-inhibitory molecules present in local environment but not the absence of regrowth.To date, three inhibitors have been identified in myelin: Myelin-Associated Glycoprotein (MAG), Nogo-A, and Oligodendrocyte-Myelin glycoprotein (OMgp). Scientists have tried to overcome myelin inhibition by delivering antibody IN-1, Nogo gene knock-out, applying Nogo antagonists and so on. But unfortunately, they did not get satisfied results. Nogo occurs in three alternative splicing forms, termed Nogo-A, Nogo-B and Nogo-C, each of which share a common C-terminal portion and a short 66 amino acid residue extracellular domain (Nogo-66). Nogo-66 has been shown to be at least partly responsible for the inhibitory activity of Nogo-A. Even though these three inhibitory proteins do not share structural similarities based on primary sequence, each binds to the Nogo receptor (NgR) to transfer signals into the neuron. It might be the result of their similar dimensional structures. NgR is a GPI-linked surface receptor so that the signals must be passed by some co-receptors. And RhoA plays an important role in this signaling pathway, for neurite outgrowth is to be blocked by increasing the level of RhoA directly or indirectly. Myelin inhibitors binding NgR will lead to the enhancement of RhoA and then activate inhibitory signaling pathway that RhoA participates in. Among these myelin inhibitors Nogo-66 contains both NgR binding and activating domains. Several small peptides derived from Nogo-66 were reported to binding NgR like agonists to break the link of the ligand and receptor so that the inhibitory signaling pathway was impressed. However, the specific regions of NgR recognizing and binding Nogo-66 are still unclear. If the...