There is currently no effective pharmacological therapy to improve the cognitive dysfunction of individuals with Down syndrome (DS). Due to the overexpression of several chromosome 21 genes, cellular and systemic oxidative stress (OS) is one of the most important neuropathological processes that contributes to the cognitive deficits and multiple neuronal alterations in DS. In this condition, OS is an early event that negatively affects brain development, which is also aggravated in later life stages, contributing to neurodegeneration, accelerated aging, and the development of Alzheimer’s disease neuropathology. Thus, therapeutic interventions that reduce OS have been proposed as a promising strategy to avoid neurodegeneration and to improve cognition in DS patients. Several antioxidant molecules have been proven to be effective in preclinical studies; however, clinical trials have failed to show evidence of the efficacy of different antioxidants to improve cognitive deficits in individuals with DS. In this review we summarize preclinical studies of cell cultures and mouse models, as well as clinical studies in which the effect of therapies which reduce oxidative stress and mitochondrial alterations on the cognitive dysfunction associated with DS have been assessed.

中文翻译：

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唐氏综合症中的抗氧化剂：从临床前研究到临床试验。

当前没有有效的药物疗法来改善唐氏综合症（DS）个体的认知功能障碍。由于一些21号染色体基因的过表达，细胞和系统的氧化应激（OS）是最重要的神经病理学过程之一，其导致DS中的认知缺陷和多种神经元改变。在这种情况下，OS是对大脑发育产生负面影响的早期事件，在以后的生命阶段也会恶化，导致神经变性，加速衰老和阿尔茨海默氏病神经病理学的发展。因此，已经提出了降低OS的治疗干预作为避免神经变性和改善DS患者认知的有前途的策略。几种抗氧化剂分子已被证明在临床前研究中是有效的。然而，临床试验未能证明不同抗氧化剂可改善DS患者认知障碍的功效。在这篇综述中，我们总结了细胞培养和小鼠模型的临床前研究以及临床研究，其中评估了减少氧化应激和线粒体改变的疗法对与DS相关的认知功能障碍的作用。