中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (5): 933-936.doi: 10.4103/1673-5374.324827

• 综述:退行性病与再生 •    下一篇

从再生策略到药理学方法:我们可以微调帕金森病的治疗吗?

  

  • 出版日期:2022-05-15 发布日期:2021-11-08

From regenerative strategies to pharmacological approaches: can we fine-tune treatment for Parkinson’s disease?

Rita Caridade Silva1, 2, Helena Sofia Domingues1, 2, António J. Salgado1, 2, Fábio G. Teixeira1, 2, *   

  1. 1Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; 2ICVS/3B’s Associate Lab, PT Government Associated Lab, Braga/Guimarães, Portugal
  • Online:2022-05-15 Published:2021-11-08
  • Contact: Fábio G. Teixeira, PhD, fabioteixeira@med.uminho.pt.
  • Supported by:
    The authors would like to acknowledge the financial support from Prémios Santa Casa Neurociências Prize Mantero Belard for Neurodegenerative Diseases Research (MB-28-2019). This work was supported by the European Regional Development Fund (FEDER), through the Competitiveness Internationalization Operational Programme (POCI), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of projects UIDB/50026/2020; UIDP/50026/2020 and POCI-01-0145-FEDER-029751. This article has also been developed under the scope of the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122) (to FGT). 

摘要: Neural Regen Res:治疗帕金森病:无干细胞策略和神经保护/疾病修饰策略的潜在结合
帕金森病是全球第二大神经退行性疾病。临床上表现为多巴胺能神经元进行性变性引起的严重运动并发症。目前的治疗主要是通过服用左旋多巴来减轻症状,而不是预防多巴胺能神经元损伤。因此,神经保护/疾病修饰策略的使用和发展是一个绝对的需要,可以在帕金森病的转化研究中带来有希望的成果。例如,一种具有强烈抗氧化作用的天然化合物N-乙酰半胱氨酸,已经被证明可以调节氧化应激,防止多巴胺诱导的细胞死亡。尽管有证据表明这种药物具有神经保护和调节作用,但它本身并不诱导任何再生过程。因此,将后者与诱导多巴胺能神经元修复甚至分化的创新疗法结合起来作为干细胞治疗策略将是一个有意义的课题。干细胞分泌体被认为是治疗帕金森病的一种很有前途的方法,因为它能够调节多巴胺能神经元的细胞活力和保存,因而基于干细胞分泌体的无细胞移植疗法可能是帕金森病再生医学的潜在替代方法。
来自葡萄牙民和大学的Fábio G. Teixeira团队认为,干细胞分泌体与潜在的神经保护/疾病修饰帕金森病药物的结合疗法可能代表了以多维方式治疗帕金森病的有效方法。事实上,单一的治疗方法(甚至是辅助治疗策略)在治疗帕金森病方面未表现出令人满意的效果,要么显示出益处(在疾病诊断后的最初几年内),要么导致不良反应(由于疾病中晚期的高剂量)。N-乙酰半胱氨酸神经保护/疾病修饰特性与干细胞分泌体再生潜能的结合可能是治疗帕金森病的多模式且有希望的方法。该治疗可依靠干细胞分泌体和N-乙酰半胱氨酸来提高受累区域多巴胺能阳性细胞的数量,解决帕金森病后多巴胺能细胞丢失和多巴胺降解作用的机制,减缓疾病进展的目的。

文章在《中国神经再生研究(英文版)》杂志2022年5月5期发表。

https://orcid.org/0000-0003-1461-9077 (Fábio G. Teixeira) 

Abstract: Parkinson’s disease is the second most prevalent neurodegenerative disorder worldwide. Clinically, it is characterized by severe motor complications caused by progressive degeneration of dopaminergic neurons. Current treatment is focused on mitigating the symptoms through the administration of levodopa, rather than on preventing dopaminergic neuronal damage. Therefore, the use and development of neuroprotective/disease-modifying strategies is an absolute need that can lead to promising gains on translational research of Parkinson’s disease. For instance, N-acetylcysteine, a natural compound with strong antioxidant effects, has been shown to modulate oxidative stress, preventing dopamine-induced cell death. Despite the evidence of neuroprotective and modulatory effects of this drug, as far as we know, it does not induce per se any regenerative process. Therefore, it would be of interest to combine the latter with innovative therapies that induce dopaminergic neurons repair or even differentiation, as stem cell-based strategies. Stem cells secretome has been proposed as a promising therapeutic approach for Parkinson’s disease, given its ability to modulate cell viability/preservation of dopaminergic neurons. Such approach represents a shift in the paradigm, showing that cell-transplantation free therapies based on the use of stem cells secretome may represent a potential alternative for regenerative medicine of Parkinson’s disease. Thus, in this review, we address the current understanding of the potential combination of stem cell free-based strategies and neuroprotective/disease-modifying strategies as a new paradigm for the treatment of central nervous system neurodegenerative diseases, like Parkinson’s disease.

Key words: disease-modifying strategies, mesenchymal stem cells, N-acetylcysteine, neuroprotection, Parkinson’s disease, stem cells secretome