中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (12): 2401-2402.doi: 10.4103/1673-5374.313027

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

少突胶质细胞介导的3R-Tau机制：中风后神经保护作用的关键吗？

  

  • 出版日期:2021-12-15 发布日期:2021-05-14

A 3R-Tau-mediated mechanism in oligodendrocytes: could it be the key for neuroprotection after stroke?

Mario Villa Gonzalez, Maria José Pérez-Álvarez*   

  1. Departamento de Biología (Fisiología Animal), Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain (Villa Gonzalez M, Pérez-Álvarez MJ);Centro de Biología Molecular “Severo Ochoa”, Departamento de Neuropatología Molecular CSIC-UAM, Madrid, Spain (Villa Gonzalez M, Pérez-Álvarez MJ);Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain (Pérez-Álvarez MJ)

  • Online:2021-12-15 Published:2021-05-14
  • Contact: Maria José Pérez-Álvarez, PhD, mj.perez@uam.es.
  • Supported by:
    This work was supported by grants from Spanish Ministry of Economy and Competitiveness (BFU-2008-03980, BFU2016-77885-P), from Comunidad de Madrid (S2017/BMD-3700) and from Departamento de Biología, Facultad de Ciencias-UAM (BIOUAM03-2020). 

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摘要：

Neural Regen Res：脑缺血后3R-Tau水平升高使少突胶质细胞的微管网络更具动态性

     一些微管网络特性受微管相关蛋白包括Tau的调节。神经元中Tau已被广泛研究，并在微管稳定中起着关键作用，但其在少突胶质细胞中的作用却鲜为人知。Tau包含通过单个基因的可变剪接产生的不同同工型；其中一些几乎不包含胚胎。异构体4R-Tau包含外显子10，具有4个微管结合域,在成熟的中枢神经系统中含量丰富，主要存在于神经元中，也存在于少突胶质细胞中，并且在微管稳定性中起重要作用。3R-Tau失去了第10外显子，并具有3个微管结合域，从而使微管更具动态性。在mRNA水平上，大脑发育过程中少突胶质细胞中3R-Tau含量丰富，但在成年人中其水平降低，而4R-Tau水平则升高。在蛋白质水平上，成年大脑中的这两种Tau亚型在call体的少突胶质细胞中显示出相似的分布。

来自西班牙马德里自治大学的Maria José Pérez-Álvarez团队发现在健康动物大脑皮层中3R-Tau也存在于某些少突胶质细胞的突起中。缺血诱导后，受损区域的少突胶质细胞中3R-Tau水平明显升高，但4RTau却没有升高。同时，少突胶质细胞中3RTau经历了向细胞突起的重新分布。尽管甲酚紫染色指出扩大的损伤区域，这些变化与缺血动物神经系统状况的改善同时发生。这些有趣的结果表明：在脑缺血后，3R-Tau水平的升高，少突胶质细胞的微管网络更具动态性。这不仅允许少突胶质细胞向缺血性受损区域迁移，而且还可以使少突胶质细胞在受损轴突中发生髓鞘形成。

文章在《中国神经再生研究（英文版）》杂志2021年12月12期发表。

https://orcid.org/0000-0001-8334-8085 (Maria José Pérez-Álvarez); 
       https://orcid.org/0000-0003-4590-5498 (Mario Villa Gonzalez)

Abstract: Cerebrovascular accident or stroke have a high global incidence. The most common types of stroke are ischemic, accounting for 87% of the total number, and they are triggered by a reduction or interruption of blood flow to the central nervous system, usually caused by a thrombus, embolus or atherosclerotic plaque. The severity of brain damage caused by this kind of stroke is directly related to the size of the vessel that is occluded and the duration of occlusion. Stroke is currently the leading cause of long-term disability worldwide and as such it has an enormous socioeconomic impact (Benjamin et al., 2019). In fact, between 30–50% of stroke patients do not recover functional independence and need personal assistance to carry out normal everyday activities. Also, according to statistics issued by the World Health Organization (WHO), ischemic stroke is the second cause of death worldwide. This year (2020) has witnessed a new cause of stroke related to coronavirus disease 2019 (COVID-19), with devastating consequences for the prognosis of this disease across all ages (García-Moncó et al., 2020). Given that the incidence of stroke increases with age and life expectancy is rising worldwide, the WHO predicts an increase in the prevalence and incidence of this condition in the coming years (Benjamin et al., 2019). The only therapeutic strategy currently used to reduce ischemic brain damage is early reperfusion using surgical methods (mechanical thrombectomy), or more frequently, the administration of a thrombolytic agent, namely the recombinant tissue plasminogen activator. However, the last approach has a therapeutic window limited to 4.5 hours after the first symptoms appear (Biggs et al., 2019). This temporal restriction implies that reperfusion is not a suitable strategy for a significant number of stroke patients due to the high risk of cerebral hemorrhage. Statistics in different countries reflect that only 10–20% of patients in acute phase of stroke, receive thrombolysis treatment (Lees et al., 2010). The remaining patients do not receive any pharmacological therapy, thus precluding the opportunity to reduce the disability and cognitive dysfunction caused by ischemia. An extension of the time window up to 24 hours has been reported for mechanical thrombectomy in certain patients (Dmytriw et al., 2019). Although reperfusion enhances the prognosis of stroke, it does not prevent the neurodegenerative processes that occur after damage. Therefore, to improve the beneficial effects of reperfusion and to enable pharmacological intervention in patients for whom this approach is not suitable, it is critical to explore alternative therapeutic strategies.