• Neuroscience · Jun 2024

    Review

    Immune System Dysregulation in the Progression of Multiple Sclerosis: Molecular Insights and Therapeutic Implications.

    • Zuber Khan, Sidharth Mehan, Ghanshyam Das Gupta, and Acharan S Narula.
    • Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab 144603, India), Moga 142001, Punjab, India.
    • Neuroscience. 2024 Jun 7; 548: 9269-26.

    AbstractMultiple sclerosis (MS), a prevalent neurological disorder, predominantly affects young adults and is characterized by chronic autoimmune activity. The study explores the immune system dysregulation in MS, highlighting the crucial roles of immune and non-neuronal cells in the disease's progression. This review examines the dual role of cytokines, with some like IL-6, TNF-α, and interferon-gamma (IFN-γ) promoting inflammation and CNS tissue injury, and others such as IL-4, IL-10, IL-37, and TGF-β fostering remyelination and protecting against MS. Elevated chemokine levels in the cerebrospinal fluid (CSF), including CCL2, CCL5, CXCL10, CXCL13, and fractalkine, are analyzed for their role in facilitating immune cell migration across the blood-brain barrier (BBB), worsening inflammation and neurodegeneration. The study also delves into the impact of auto-antibodies targeting myelin components like MOG and AQP4, which activate complement cascades leading to further myelin destruction. The article discusses how compromised BBB integrity allows immune cells and inflammatory mediators to infiltrate the CNS, intensifying MS symptoms. It also examines the involvement of astrocytes, microglia, and oligodendrocytes in the disease's progression. Additionally, the effectiveness of immunomodulatory drugs such as IFN-β and CD20-targeting monoclonal antibodies (e.g., rituximab) in modulating immune responses is reviewed, highlighting their potential to reduce relapse rates and delaying MS progression. These insights emphasize the importance of immune system dysfunction in MS development and progression, guiding the development of new therapeutic strategies. The study underscores recent advancements in understanding MS's molecular pathways, opening avenues for more targeted and effective treatments.Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.

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