中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (9): 1413-1415.doi: 10.4103/1673-5374.165308

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

超兴奋性是肌萎缩侧索硬化症的“真凶”么?

  

  • 收稿日期:2015-05-29 出版日期:2015-09-28 发布日期:2015-09-28

Is hyperexcitability really guilty in amyotrophic lateral sclerosis?

Felix Leroy, Daniel Zytnicki   

  1. Centre de Neurophysique, Physiologie et Pathologie, UMR 8119, Université Paris Descartes, UMR 8119, 45 rue des
    Saints-Pères, 752070 Paris Cedex 06, France
  • Received:2015-05-29 Online:2015-09-28 Published:2015-09-28
  • Contact: Felix Leroy, Ph.D., fl2379@columbia.edu.
  • Supported by:

    Financial supports provided by the Agence Nationale pour la Recherche (HYPER-MND, ANR-2010-BLAN-1429-01), the NIH-NINDS (R01NS077863), the Thierry Latran Fundation (OHEX Project) and Target ALS are gratefully acknowledged. Felix Leroy was recipient of a “Contrat Doctoral” from the Ecole Normale Supérieure, Cachan.
    The authors would like to thank Philippe Ascher, Arjun Masurkar and Georges mentis and for their corrections and advice.

摘要:

肌萎缩性侧索硬化症是一种致命疾病,特征是脑干和脊髓运动神经元以及横向皮质脊髓束的逐步退化,在成年人中发病率较高。直到最近,90%的该病病例被认为是偶发性的。其中SOD1基因突变在很长一段时间内是已报道的肌萎缩性侧索硬化症唯一熟悉的发病机制。最近一些鲜为人知的新基因功能为本病提供了新视角。例如,C9ORF72现在被认为是导致30%家族性病例的病因。总体而言,肌萎缩性侧索硬化症与20个不同的基因有关,其中的许多基因也关联到其他退行性疾病(额颞痴呆,早老性痴呆或共济失调)。人类患者和小鼠模型的临床观察表明,所有运动池和运动神经元不会受到的影响不全相同。这种疾病通常开始于运动池控制肢体或延髓区域扩大到其他运动池。运动神经元支配慢运动单位出现抵抗疾病现象。虽然导致有序变性的机制尚不清楚许多假说已经提出。

Abstract:

Amyotrophic lateral sclerosis (ALS) is a lethal disorder characterized by the gradual degeneration of brainstem and spinal motoneurons as well as lateral cortico-spinal tracts. The onset generally occurs during the adult age except for some juvenile aggressive forms. Until recently, the vast majority of the cases (90%) were deemed sporadic. Mutations in the SOD1 gene have been for a long time the only ones reported in familiar forms of ALS. The recent implication of new genes of little known function cast a new view on this disease. C9ORF75, for example, is now recognized to account for 30% of the familial cases. Overall, ALS has been linked to 20 different genes, many also associated with other degenerative diseases (frontotemporal dementia, Alzheimer or ataxia). Some of these genes are involved in RNA maturation (FUS, TARBD). Clinical observation of human patients and mouse models suggest that all motor pools and motoneurons are not equally affected. The disease usually starts in motor pools controlling the limbs or in the bulbar area before expanding to other motor pools, with the exception of a few resistant ones (Onuf’s and oculomotor nuclei). Within a vulnerable motor pool, motoneurons subtypes also exhibit differential vulnerability and follow an orderly degeneration; starting with the motoneurons innervating fast-contracting fatigable motor units (FF motoneurons) and followed by the ones innervating fast-contractile fatigue-resistant motor units (FR motoneurons). The motoneurons innervating slow motor units (S motoneurons) appear resistant to the disease. Although the mechanisms leading to the orderly degeneration are not known, many hypotheses have been raised.