The protein product of RGMA, RGMa, is a glycosylphosphatidylinosital-anchored glycoprotein that exists in membrane-bound and soluble forms (29), both of which are potent regulators of cell death and inhibitors of nerve growth. RGMa was first reported to be a developmental neurite growth inhibitor (30). It has since emerged as an important factor inhibiting neuronal regeneration and functional recovery (31, 32). RGMa inhibits neurite growth by binding to its neuronal receptor, neogenin, a member of the immunoglobulin (Ig) superfamily. Neogenin overexpression and RGMa down expression in the developing embryonic neural tube induce apoptosis (33). RGMa may be involved in neuroplasticity consistent with increased secretion of RGMa in stroke- or injury-damaged human brain tissue (34), in the plaque regions of Alzheimer's disease patients (35), in the substantia nigra of Parkinson's disease patients (36), and in multiple sclerosis (MS) patients (37). Considering the example of progressive MS (38), RGMa was found in active and chronic lesions, and in normal-appearing gray and white matter, and was expressed by cellular meningeal infiltrates in autopsy material. Levels of soluble RGMa in the cerebrospinal fluid were decreased
