中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (8): 1366-1367.doi: 10.4103/1673-5374.235242

• 观点:退行性病与再生 • 上一篇    下一篇

用于多发性硬化症中神经再生的药物重新使用

  

  • 收稿日期:2018-06-02 出版日期:2018-08-15 发布日期:2018-08-15

Drug repurposing for neuroregeneration in multiple sclerosis

Patrick Küry, David Kremer, Peter Göttle   

  1. Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
  • Received:2018-06-02 Online:2018-08-15 Published:2018-08-15
  • Contact: Peter G?ttle, Ph.D.,Peter.Goettle@uni-duesseldorf.de.
  • Supported by:

    Cited research work in the laboratory of the authors was supported by the Jürgen Manchot Foundation Düsseldorf, by the research commission of the medical faculty of Heinrich-Heine-University of Düsseldorf and by a grant of Sanofi Genzyme. The MS Center at the Department of Neurology is supported in part by the Walter and Ilse Rose Foundation and the James and Elisabeth Cloppenburg, Peek & Cloppenburg Düsseldorf Stiftung.

摘要:

orcid: 0000-0001-6830-0956 (Peter Göttle)
         0000-0002-2654-1126 (Patrick Küry)

Abstract:

Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease of the central nervous system (CNS) affecting at least 2.5 million people worldwide. While the relapsing subtypes of MS are well treatable, the disease per se remains incurable and results in progressive disability. Its etiology is complex and far from being understood. However,it is well-established that its central histopathological hallmark is demyelination - the autoimmune destruction of myelin sheaths. These elaborate structures wrap around axons electrically isolating them and provide accelerated electrical transmission as well as physical and trophic support in the brain and spinal cord. Demyelination impairs axonal integrity which leads to permanent disability. Whereas relapsing MS (RMS) which is most common at disease onset is characterized by episodes of autoimmune attacks (relapse) followed by spontaneous partial functional recovery (remission), most patients eventually develop a progressive disease course. Progressive MS stages, however, are mainly characterized by reduced or absent immune cell infiltration but ongoing neurodegeneration.Neuroregeneration in MS, on the other hand, basically refers to myelin repair - a process that can repair some of the existing lesions via recruitment of resident oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) which can differentiate and produce new axonal myelin sheaths restoring axonal integrity. However, the repair capacity of precursor- and stem cells declines with age and disease progression. Moreover,differences in the extent of myelin regeneration can be observed between lesions and patients, potentially indicating heterogeneous underlying mechanisms which interfere with myelin restoration.In this regard, several oligodendroglial differentiation inhibitors have been identified which are supposed to prevent successful cell maturation in an inflammatory environment.