Güner Fabian, Rothhammer Veit
Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany.
Front Immunol. 2025 Aug 27;16:1654603. doi: 10.3389/fimmu.2025.1654603. eCollection 2025.
Smoldering inflammation and neurodegeneration, primarily driven by intraparenchymal immune cell activation and glial dysfunction, remains a major therapeutic challenge in Multiple Sclerosis (MS) and contributes largely to disability progression. Current disease-modifying therapies effectively decrease relapse rate and, to a lesser extent, disease progression by targeting peripheral immune cells. However, they largely fail to address Central-Nervous-System-(CNS)-intrinsic pathological processes - especially glial dysfunction - thus leaving a critical gap relevant to disease progression and therapeutic intervention. In this context, neurotrophic factors (NTF) are secreted proteins central for development and maintenance of the CNS. They promote anti-inflammatory, protective phenotypes in astrocytes and microglia, support remyelination by enhancing oligodendrocyte precursor recruitment, maturation and survival, and exert direct neuroprotective effects. Exploring their role in MS offers a novel perspective on neuroimmune crosstalk and prevention of progressive neurodegeneration. In this article, we summarize relevant findings on NTFs in MS, and give an outlook on opportunities and challenges of using these mediators as next-generation disease-modifying therapies.
主要由脑实质内免疫细胞激活和胶质细胞功能障碍驱动的隐匿性炎症和神经退行性变，仍然是多发性硬化症（MS）治疗的主要挑战，并且在很大程度上导致残疾进展。目前的疾病修饰疗法通过靶向外周免疫细胞有效地降低了复发率，并在较小程度上减缓了疾病进展。然而，它们在很大程度上未能解决中枢神经系统（CNS）内在的病理过程，尤其是胶质细胞功能障碍，从而在疾病进展和治疗干预方面留下了关键差距。在这种背景下，神经营养因子（NTF）是对CNS的发育和维持至关重要的分泌蛋白。它们促进星形胶质细胞和小胶质细胞的抗炎、保护表型，通过增强少突胶质细胞前体细胞的募集、成熟和存活来支持髓鞘再生，并发挥直接的神经保护作用。探索它们在MS中的作用为神经免疫相互作用和预防进行性神经退行性变提供了新的视角。在本文中，我们总结了MS中NTF的相关研究结果，并展望了将这些介质用作下一代疾病修饰疗法的机遇和挑战。
