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间充质干细胞在对抗氧化应激相关神经退行性变中的作用。

Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress-Related Neurodegeneration.

机构信息

School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy.

Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy.

出版信息

Int J Mol Sci. 2020 May 7;21(9):3299. doi: 10.3390/ijms21093299.

Abstract

Neurodegenerative diseases include a variety of pathologies such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and so forth, which share many common characteristics such as oxidative stress, glycation, abnormal protein deposition, inflammation, and progressive neuronal loss. The last century has witnessed significant research to identify mechanisms and risk factors contributing to the complex etiopathogenesis of neurodegenerative diseases, such as genetic, vascular/metabolic, and lifestyle-related factors, which often co-occur and interact with each other. Apart from several environmental or genetic factors, in recent years, much evidence hints that impairment in redox homeostasis is a common mechanism in different neurological diseases. However, from a pharmacological perspective, oxidative stress is a difficult target, and antioxidants, the only strategy used so far, have been ineffective or even provoked side effects. In this review, we report an analysis of the recent literature on the role of oxidative stress in Alzheimer's and Parkinson's diseases as well as in amyotrophic lateral sclerosis, retinal ganglion cells, and ataxia. Moreover, the contribution of stem cells has been widely explored, looking at their potential in neuronal differentiation and reporting findings on their application in fighting oxidative stress in different neurodegenerative diseases. In particular, the exposure to mesenchymal stem cells or their secretome can be considered as a promising therapeutic strategy to enhance antioxidant capacity and neurotrophin expression while inhibiting pro-inflammatory cytokine secretion, which are common aspects of neurodegenerative pathologies. Further studies are needed to identify a tailored approach for each neurodegenerative disease in order to design more effective stem cell therapeutic strategies to prevent a broad range of neurodegenerative disorders.

摘要

神经退行性疾病包括多种病理学,如阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症等,它们具有许多共同的特征,如氧化应激、糖化、异常蛋白沉积、炎症和进行性神经元丧失。上个世纪见证了大量的研究,以确定导致神经退行性疾病复杂病因发病机制和风险因素,如遗传、血管/代谢和生活方式相关因素,这些因素经常共同发生并相互作用。除了一些环境或遗传因素外,近年来,大量证据表明,氧化还原平衡的损害是不同神经疾病的共同机制。然而,从药理学的角度来看,氧化应激是一个难以攻克的靶点,抗氧化剂是迄今为止唯一使用的策略,其效果不佳甚至引发了副作用。在这篇综述中,我们报告了对氧化应激在阿尔茨海默病和帕金森病以及肌萎缩侧索硬化症、视网膜神经节细胞和共济失调中的作用的最新文献的分析。此外,干细胞的作用也得到了广泛的探索,研究了它们在神经元分化中的潜力,并报告了它们在不同神经退行性疾病中对抗氧化应激的应用的发现。特别是,间充质干细胞或其分泌组的暴露可以被认为是一种有前途的治疗策略,以增强抗氧化能力和神经营养因子的表达,同时抑制促炎细胞因子的分泌,这是神经退行性疾病的共同特征。需要进一步的研究来为每种神经退行性疾病确定一种针对性的方法,以设计更有效的干细胞治疗策略,预防广泛的神经退行性疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ee7/7246730/4f2bda8a7a5f/ijms-21-03299-g001.jpg

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