中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (8): 1247-1251.doi: 10.4103/1673-5374.213538

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

LINGO-1和AMIGO3:脱髓鞘疾病的潜在治疗靶点?

  

  • 收稿日期:2017-07-17 出版日期:2017-08-15 发布日期:2017-08-15
  • 基金资助:

    此项研究得到了英国伯明翰大学的赞助支持

LINGO-1 and AMIGO3, potential therapeutic targets for neurological and dysmyelinating disorders?

Simon Foale, Martin Berry, Ann Logan, Daniel Fulton, Zubair Ahmed   

  1. Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
  • Received:2017-07-17 Online:2017-08-15 Published:2017-08-15
  • Contact: Zubair Ahmed, Ph.D.,z.ahmed.1@bham.ac.uk.
  • Supported by:

    This work was supported by a grant from The University of Birmingham.

摘要:

由于在中枢神经系统中的表达和生物活性,亮氨酸重复(LRR)蛋白质作为治疗靶点已经得到了研究者的广泛关注。LINGO-1受到特别关注是因为它以RhoA依赖的方式抑制脊髓损伤后的轴突再生,同时抑制神经元生长。此外,LINGO-1还会抑制少突胶质细胞前体细胞(OPC)成熟和髓磷脂生成。抑制LINGO-1的作用有利于髓鞘再生。因此,LINGO-1拮抗剂是有希望的脱髓鞘疾病治疗方法。与LINGO-1类似的蛋白质AMIGO3对CNS神经元的轴突生长发挥相同的抑制作用,并且与LINGO-1相同的受体相互作用。然而,AMIGO3在脊髓损伤后比LINGO-1更快地上调。因此,抑制AMIGO3可能会促进CNS轴突再生以及从局部OPC产生髓磷脂,从而为脱髓鞘疾病的治疗提供有希望的治疗靶点。

orcid:0000-0001-6267-6492(Zubair Ahmed)

Abstract:

Leucine rich repeat proteins have gained considerable interest as therapeutic targets due to their expression and biological activity within the central nervous system. LINGO-1 has received particular attention since it inhibits axonal regeneration after spinal cord injury in a RhoA dependent manner while inhibiting  leucine rich repeat and immunoglobulin-like domain-containing protein 1 (LINGO-1) disinhibits neuron outgrowth. Furthermore, LINGO-1 suppresses oligodendrocyte precursor cell maturation and myelin production. Inhibiting the action of LINGO-1 encourages remyelination both in vitro and in vivo. Accordingly, LINGO-1 antagonists show promise as therapies for demyelinating diseases. An analogous protein to LINGO-1, amphoterin-induced gene and open reading frame-3 (AMIGO3), exerts the same inhibitory effect on the axonal outgrowth of central nervous system neurons, as well as interacting with the same receptors as LINGO-1. However, AMIGO3 is upregulated more rapidly after spinal cord injury than LINGO-1 . We speculate that AMIGO3 has a similar inhibitory effect on oligodendrocyte precursor cell maturation and myelin production as with axogenesis. Therefore, inhibiting AMIGO3 will likely encourage central nervous system axonal regeneration as well as the production of myelin from local oligodendrocyte precursor cell, thus providing a promising therapeutic target and an area for future investigation.

Key words: multiple sclerosis, demyelination, oligodendrocyte, AMIGO3, LINGO1, oligodendrocyte precursor cell