The oxidative stress-inflammation self-perpetuating cycle in multiple sclerosis: from mechanisms to emerging...

Multiple sclerosis (MS) is a complex multifactorial disease of the central nervous system (CNS) whose pathogenesis has not yet been fully elucidated. Current MS treatments primarily consist of disease-modifying therapies with anti-inflammatory and immunomodulatory properties, which effectively reduce relapse rates and disease activity. However, these therapies often exhibit limited long-term efficacy, may cause severe adverse effects, and remain largely insufficient in preventing the progressive accumulation of irreversible disability driven by axonal and neuronal damage. Although oxidative stress (OS) is not the sole pathologic factor in MS, substantial evidence supports its critical contribution to disease development and progression. In particular, OS is closely associated with key pathological processes such as demyelination and axonal degeneration. OS can act as a signaling mediator that promotes inflammatory responses, while inflammatory processes further amplify OS, forming a self-perpetuating cycle that exacerbates CNS tissue injury. Consequently, increasing attention has been directed toward the development of antioxidant-based therapeutic strategies for MS. Nevertheless, a comprehensive synthesis of MS drug development from the perspective of antioxidant capacity remains lacking, limiting rational therapeutic. This review examines the interplay between inflammation and OS in MS pathology, and summarizes current advances in antioxidant-based therapeutic approaches. By integrating existing evidence, this work aims to clarify the role of OS in MS pathogenesis and to inform the development of effective antioxidant-oriented treatments.