Bjørklund Geir, Wallace David R, Hangan Tony, Butnariu Monica, Gurgas Leonard, Peana Massimiliano
Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway.
Department of Pharmacology, Oklahoma State University Center for Health Sciences, Tulsa, OK, United States.
Autoimmun Rev. 2025 Mar 26;24(4):103741. doi: 10.1016/j.autrev.2025.103741. Epub 2025 Jan 3.
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by demyelination, neuroinflammation, and neurodegeneration. Recent studies highlight the role of cerebral iron (Fe) accumulation in exacerbating MS pathophysiology. Fe, essential for neural function, contributes to oxidative stress and inflammation when dysregulated, particularly in the brain's gray matter and demyelinated lesions. Advanced imaging techniques, including susceptibility-weighted and quantitative susceptibility mapping, have revealed abnormal Fe deposition patterns in MS patients, suggesting its involvement in disease progression. Iron's interaction with immune cells, such as microglia, releases pro-inflammatory cytokines, further amplifying neuroinflammation and neuronal damage. These findings implicate Fe dysregulation as a significant factor in MS progression, contributing to clinical manifestations like cognitive impairment. Therapeutic strategies targeting Fe metabolism, including Fe chelation therapies, show promise in reducing Fe-related damage, instilling optimism about the future of MS treatment. However, challenges such as crossing the blood-brain barrier and maintaining Fe homeostasis remain. Emerging approaches, such as Fe-targeted nanotherapeutics and biologics, offer new possibilities for personalized treatments. However, the journey is far from over. Continued research into the molecular mechanisms of Fe-induced neuroinflammation and oxidative damage is essential. Through this research, we can develop effective interventions that could slow MS progression and improve patient outcomes.
多发性硬化症（MS）是一种中枢神经系统的慢性自身免疫性疾病，其特征为脱髓鞘、神经炎症和神经退行性变。最近的研究强调了脑铁（Fe）蓄积在加重MS病理生理过程中的作用。铁对神经功能至关重要，但当调节失调时，尤其在脑灰质和脱髓鞘病变中，会导致氧化应激和炎症。包括磁敏感加权成像和定量磁敏感成像在内的先进成像技术已揭示MS患者存在异常的铁沉积模式，表明其与疾病进展有关。铁与免疫细胞（如小胶质细胞）的相互作用会释放促炎细胞因子，进一步加剧神经炎症和神经元损伤。这些发现表明铁调节失调是MS进展的一个重要因素，导致认知障碍等临床表现。针对铁代谢的治疗策略，包括铁螯合疗法，在减少铁相关损伤方面显示出前景，为MS治疗的未来带来了乐观的希望。然而，仍存在诸如穿越血脑屏障和维持铁稳态等挑战。新兴方法，如铁靶向纳米疗法和生物制剂，为个性化治疗提供了新的可能性。然而，这一旅程远未结束。持续研究铁诱导神经炎症和氧化损伤的分子机制至关重要。通过这项研究，我们可以开发出有效的干预措施，减缓MS进展并改善患者预后。
