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Despite recognition as an early indicator, the mechanisms driving optic neuritis and its contribution to MS progression remain unclear. Traditionally, immune-mediated inflammation has dominated MS research; however, emerging evidence highlights neurotransmitter dysregulation\u2014especially involving dopamine\u2014as a crucial factor in disease pathophysiology. The impact of dopamine imbalance on neural circuits and its role in advancing MS requires further investigation. This paper proposes a system-level, dopamine-based hypothesis to explain MS origins, focusing on early stages in CIS. Building on a review of recent literature linking dopaminergic dysfunction, neuroinflammation, and demyelination, the model suggests that optic nerve demyelination, as seen in optic neuritis, disrupts dopamine signaling, triggering a cascade of neural alterations that drive MS pathogenesis. By emphasizing dopamine role in CIS and early MS, this framework offers a novel perspective on the neurobiological mechanisms underlying the disease. This approach complements current research on neurotransmitter involvement in age-related conditions, expanding understanding of how neurotransmitter imbalances may influence MS and related disorders.<\/jats:p>","DOI":"10.3389\/fneur.2025.1653134","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:12:42Z","timestamp":1758784362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["System-level hypothesis of dopamine imbalance in early multiple 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