Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response.
Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response.
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DOI：
10.5501/wjv.v4.i3.188
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发表时间：
2015-08-12
期刊：
影响因子：
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通讯作者：
Thackray, Alana M
中科院分区：
文献类型：
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作者：
Bujdoso, Raymond;Landgraf, Matthias;Thackray, Alana M
蛋白质错误折叠神经退行性疾病是通过宿主蛋白质聚集诱导的神经毒性而产生的。这些病症包括阿尔茨海默病、亨廷顿病、帕金森病、运动神经元病、tau蛋白病和朊病毒病。总的来说，由于老龄人口的增加以及动物朊病毒疾病对人类粮食安全的真实的威胁，这些条件对社会构成挑战。因此，重要的是要了解蛋白质错误折叠诱导的神经毒性的细胞和分子机制，因为这将成为设计减轻其负担的策略的基础。一般来说，朊病毒疾病是神经退行性疾病的一个重要范例，因为其中几种疾病现已被证明表现出朊病毒样现象。越来越多地，细胞周期活动和DNA损伤反应被认为是参与各种神经退行性疾病及其相关动物模型的神经毒性过程的细胞事件，这表明它们确实参与了致病过程，而不仅仅是附带现象。在这里，我们回顾了细胞周期活动和DNA损伤反应在与蛋白质错误折叠疾病相关的神经变性中的作用，并建议这些事件有助于朊病毒诱导的神经毒性。在这样做时，我们强调PrP转基因果蝇作为一个易于处理的模型，遗传分析的传染性哺乳动物朊病毒疾病。
Protein misfolding neurodegenerative diseases arise through neurotoxicity induced by aggregation of host proteins. These conditions include Alzheimer's disease, Huntington's disease, Parkinson's disease, motor neuron disease, tauopathies and prion diseases. Collectively, these conditions are a challenge to society because of the increasing aged population and through the real threat to human food security by animal prion diseases. It is therefore important to understand the cellular and molecular mechanisms that underlie protein misfolding-induced neurotoxicity as this will form the basis for designing strategies to alleviate their burden. Prion diseases are an important paradigm for neurodegenerative conditions in general since several of these maladies have now been shown to display prion-like phenomena. Increasingly, cell cycle activity and the DNA damage response are recognised as cellular events that participate in the neurotoxic process of various neurodegenerative diseases, and their associated animal models, which suggests they are truly involved in the pathogenic process and are not merely epiphenomena. Here we review the role of cell cycle activity and the DNA damage response in neurodegeneration associated with protein misfolding diseases, and suggest that these events contribute towards prion-induced neurotoxicity. In doing so, we highlight PrP transgenic Drosophila as a tractable model for the genetic analysis of transmissible mammalian prion disease.