Myelin and Oligodendrocyte Dysfunction in Demyelinating and Neurodegenerative Disorders: Signaling Pathways and Therapeutic Targets.
TL;DR
Myelin integrity and oligodendrocyte function are central to the progression of demyelinating and neurodegenerative diseases and targeting molecular pathways involved in myelination offers significant potential for improving disease outcomes and developing advanced therapeutic strategies.
Abstract
INTRODUCTION Oligodendrocytes (OLs) synthesize myelin, a substance that plays a significant role in ensuring proper functioning of the Central Nervous System (CNS). Myelin abnormalities are involved in disease pathogenesis in AD, MS, and ALS. In contrast, MS involves autoimmune reactions directed against myelin. On the other hand, AD and ALS are characterized by neurodegeneration. This article seeks to give a critical discussion on myelin and OL dysfunction in these diseases, among others.
Methods
A narrative literature search was carried out in various databases including Scopus, Google Scholar, Web of Science, and PubMed, focusing on papers relating to myelination, remyelination, and OLs, particularly those addressing signaling pathways and treatment strategies.
Results
MS is an autoimmune disease characterized by inflammation that causes demyelination and OL dysfunction. Oxidative stress and mitochondrial dysfunction play roles in the pathogenesis of ALS, whereas AD is a result of disrupted neuronal supportive functions and myelin damage. Important signaling pathways involved in OL formation and myelin repair include the Wnt/β-catenin, AKT/mTOR, and ERK/MAPK pathways. Drugs like edaravone, ocrelizumab, and siponimod have been identified for promoting myelin repair.
Discussion
The relationship between abnormal oligodendrocyte function, demyelination, and specific disease-related pathological processes demonstrates that although there is a similarity among MS, AD, and ALS, each condition possesses its own unique molecular foundation. One potential treatment approach would be targeting shared signaling pathways relevant to myelination and remyelination. Nonetheless, disease variability and specific pathogenic characteristics demand a targeted therapy approach.
Conclusion
Myelin integrity and oligodendrocyte function are central to the progression of demyelinating and neurodegenerative diseases. Targeting molecular pathways involved in myelination offers significant potential for improving disease outcomes and developing advanced therapeutic strategies.