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Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia

机译:氧化应激和唐氏综合症:迈向痴呆症的途径

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摘要

Down syndrome (DS) is one of the most frequent genetic abnormalities characterized by multiple pathological phenotypes. Indeed, currently life expectancy and quality of life for DS patients have improved, although with increasing age pathological dysfunctions are exacerbated and intellectual disability may lead to the development of Alzheimer's type dementia (AD). The neuropathology of DS is complex and includes the development of AD by middle age, altered free radical metabolism, and impaired mitochondrial function, both of which contribute to neuronal degeneration. Understanding the molecular basis that drives the development of AD is an intense field of research. Our laboratories are interested in understanding the role of oxidative stress as link between DS and AD. This review examines the current literature that showed oxidative damage in DS by identifying putative molecular pathways that play a central role in the neurodegenerative processes. In addition, considering the role of mitochondrial dysfunction in neurodegenerative phenomena, results demonstrating the involvement of impaired mitochondria in DS pathology could contribute a direct link between normal aging and development of AD-like dementia in DS patients.
机译:唐氏综合症(DS)是最常见的遗传异常之一,其特征是多种病理表型。实际上,尽管随着年龄的增长,病理功能障碍加重,智力障碍可能导致阿尔茨海默氏痴呆症(AD)的发展,但DS患者的预期寿命和生活质量已有所改善。 DS的神经病理学很复杂,包括中年人AD的发展,自由基代谢的改变和线粒体功能的受损,这两者均导致神经元变性。了解驱动AD发展的分子基础是一个研究热点。我们的实验室有兴趣了解氧化应激在DS和AD之间的作用。这篇综述通过鉴定在神经变性过程中起关键作用的假定分子途径,研究了在DS中显示出氧化损伤的现有文献。此外,考虑到线粒体功能障碍在神经退行性现象中的作用,表明线粒体受损参与DS病理学的结果可能有助于DS患者正常衰老与AD样痴呆发展之间的直接联系。

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