Repulsive Guidance Molecule-a and Central Nervous System Diseases.

Jinhua Tang,Jun Yang,Hang Li,Lu Ju,Jinzhou Feng,Xiaopeng Zeng,Yuzhen Xu

doi:10.1155/2021/5532116

Abstract

Repulsive guidance molecule-a (RGMa) is a member of glycosylphosphatidylinositol- (GPI-) anchored protein family, which has axon guidance function and is widely involved in the development and pathological processes of the central nervous system (CNS). On the one hand, the binding of RGMa and its receptor Neogenin can regulate axonal guidance, differentiation of neural stem cells into neurons, and the survival of these cells; on the other hand, RGMa can inhibit functional recovery of CNS by inhibiting axonal growth. A number of studies have shown that RGMa may be involved in the pathogenesis of CNS diseases, such as multiple sclerosis, neuromyelitis optica spectrum diseases, cerebral infarction, spinal cord injury, Parkinson's disease, and epilepsy. Targeting RGMa can enhance the functional recovery of CNS, so it may become a promising target for the treatment of CNS diseases. This article will comprehensively review the research progression of RGMa in various CNS diseases up to date.

Highlights

Repulsive guidance molecule-a (RGMa) is a member of glycosylphosphatidylinositol (GPI)-anchored protein family [1]
Other scholars believe that the combination of RGMa and Neogenin affects the survival of neurons in the central nervous system (CNS) through deathassociated protein kinase (DAPK) and LIM protein 4 (LMO4)
We found that RGMa can inhibit axonal growth by phosphorylating collapse response mediator protein-2 (CRMP-2) through the Rho kinase and glycogen synthase kinase 3 β (GSK-3β) signaling pathways (Table 1) [51, 52]

Summary

Introduction

RGMa (repulsive guidance molecule-a) is a member of glycosylphosphatidylinositol (GPI)-anchored protein family [1]. It was first found in the visual system of chicken embryo, with axon guidance function [1]. RGMa exists in CNS such as neural stem cells, neuron cells, and myelin sheath in both soluble and membrane-bound forms [4, 5]. It binds with type I transmembrane protein Neogenin and plays the biological functions of axon guidance and neuron survival through the FAK-RhoA signaling pathway [4, 5]. These data indicated that RGMa may be involved in the pathogenesis of the above diseases and may become a potential target for the treatment of CNS diseases

Role of RGMa in CNS Physiology

Role of RGMa in CNS Pathology

RGMa as a Therapeutic Target in CNS Disorders

Participants or models

Summary

Conflicts of Interest