Unlocking the Therapeutic Potential of Rgma: A New Frontier in Neurological Disorder Treatment Publisher Pubmed



Hosseini E ; Sahraian MA ; Negah SS
Source: Molecular Neurobiology Published:2026

Abstract

Finding new biomolecules to target upstream signaling in neurological disorders is a state-of-the-art research strategy. Axon guidance molecules (AGMs) play vital roles in development; however, evidence suggests that these molecules are involved in the pathogenesis of several neurological diseases. Recent studies have shown that repulsive guidance molecule A (RGMa), a member of AGMs, can be targeted as a novel therapeutic option. This molecule has been implicated in several diseases, and inhibiting it improves the outcomes. For example, in various pathological conditions such as multiple sclerosis, neuromyelitis optica, optic nerve crush model, focal cerebral ischemia, traumatic brain injury, and vascular dementia the expression of RGMa is significantly elevated. RGMa has been detected on amyloid plaques and in the glial scar in brains impacted by Alzheimer’s disease. Furthermore, RGMa is elevated by activated astrocytes after exposure to TGFβ. Since the role of RGMa in the development of neurological disorders is crucial, inhibiting RGMa can lead to positive outcomes such as axonal regeneration, neuronal repair, and behavioral improvement. Our review explores the impact of RGMa and outlines the positive results achieved by targeting it in preclinical studies. Based on this information, it is clear that RGMa has significant potential as both a predictive biomarker and a therapeutic option. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.