中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (11): 1761-1763.doi: 10.4103/1673-5374.165294

• 观点:退行性病与再生 • 上一篇    下一篇

多发性硬化症患者白介素16和轴突退变之间的联系

  

  • 收稿日期:2015-07-20 出版日期:2015-12-07 发布日期:2015-12-07

Chemotactic signaling and beyond: link between interleukin-16 and axonal degeneration in multiple sclerosis

Dusanka S. Skundric*   

  1. Department of Immunology and Microbiology, School of Medicine, Wayne State University, Detroit, MI, USA
  • Received:2015-07-20 Online:2015-12-07 Published:2015-12-07
  • Contact: Dusanka S. Skundric, Ph.D.,Skundric@wayne.edu.

摘要:

多发性硬化症是一种进行性炎性及慢性脱髓鞘的中枢神经系统的退行性疾病。自身免疫T细胞从周围淋巴器官迁移至中枢神经系统导致了炎症、脱髓鞘以及轴突细胞骨架损伤,表现为运动及感觉神经脉冲传导速度下降。髓鞘以及轴突的病理变化引发运动神经、感觉神经及自主神经功能障碍,包括轻瘫、肢体瘫痪、疼痛反应以及膀胱括约肌功能障碍(表现为失禁)。而位于皮质和皮质下区的神经灰质也可以出现病理表现,包括小脑和海马体引发的如记忆减退、抑郁以及步态失调等其他认知和行为功能障碍。关于实验性自身免疫性脑脊髓炎细胞和分子机制涉及的多种自身免疫介导炎症、脱髓鞘以及随后的轴突细胞骨架退化以及神经细胞功能障碍及死亡已有许多的研究证实。随着新的实验性自身免疫性脑脊髓炎模型的发展,实验性自身免疫性脑脊髓炎在多发性硬化症研究领域的重要性将继续得到重复验证,并且两种疾病相似点的重要性也将被重视起来。自身免疫实验模型经常被用于多发性硬化症治疗的临床前试验中,目的是治疗或改善多发性硬化症中观察到的自身免疫应答,最终达到治愈或减少组织损伤并且支持轴突再生及修复的目标。

Abstract:

Multiple sclerosis (MS) is progressive inflammatory, and chronic demyelinating, neurodegenerative disease of central nervous system (CNS). Autoimmune responses to myelin and other CNS antigens mediated by CD4+ T cells are critical for initiation and progression of disease.Migration of autoimmune T cells from the peripheral lymph organs into CNS parenchyma leads to inflammation, demyelination and damage of axonal cytoskeleton, which manifest indecreased impulse conduction velocity of motor and sensory nerves. Myelin and axonal pathology causes motor, sensory and autonomic nerve dysfunction, including paresis and paralysis of extremities, painful sensations, and bladder sphincter dysfunction, manifested as incontinence. Gray matter pathology in cortical and subcortical regions, including cerebellum and hippocampus underlies cognitive and behavioral dysfunctioncomprisingof among other, memory deficits, depression, and ataxic gait. Multifaceted cellular and molecular mechanisms involved in autoimmune – mediated inflammation, demyelination, and subsequent degeneration of axonal cytoskeleton as well asneuronal cell dysfunction and demise, have been researched in experimental autoimmune encephalomyelitis (EAE). With the development of new EAE models, significance of EAE in MS studies continues to be reexamined and the importance of similarity between two diseases to be highlighted. This autoimmune experimental model is regularly used in development and preclinical testing of MS therapy aimed at treating or ameliorating autoimmune responses observed in MS, with an ultimate goal to cure or diminish tissue damage and support axonal regeneration and repair.