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首页> 外文期刊>Neuron >Selective neuronal vulnerability in neurodegenerative diseases: from stressor thresholds to degeneration.
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Selective neuronal vulnerability in neurodegenerative diseases: from stressor thresholds to degeneration.

机译：神经退行性疾病中的选择性神经元脆弱性：从应激阈值到变性。

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摘要

Neurodegenerative diseases selectively target subpopulations of neurons, leading to the progressive failure of defined brain systems, but the basis of such selective neuronal vulnerability has remained elusive. Here, we discuss how a stressor-threshold model of how particular neurons and circuits are selectively vulnerable to disease may underly the etiology of familial and sporadic forms of diseases such as Alzheimer's, Parkinson's, Huntington's, and ALS. According to this model, the intrinsic vulnerabilities of neuronal subpopulations to stressors and specific disease-related misfolding proteins determine neuronal morbidity. Neurodegenerative diseases then involve specific combinations of genetic predispositions and environmental stressors, triggering increasing age-related stress and proteostasis dysfunction in affected vulnerable neurons. Damage to vasculature, immune system, and local glial cells mediates environmental stress, which could drive disease at all stages.
机译：神经退行性疾病选择性地靶向神经元的亚群，导致确定的脑系统进行性衰竭，但是这种选择性神经元易损性的基础仍然难以捉摸。在这里，我们讨论特定神经元和回路如何选择性地易受疾病侵害的应激阈模型可能会在诸如阿尔茨海默氏病，帕金森氏病，亨廷顿氏病和ALS等家族性和散发性疾病的病因学上产生潜在影响。根据该模型，神经元亚群对应激源和与疾病相关的错误折叠蛋白的固有脆弱性决定了神经元发病率。然后，神经退行性疾病涉及遗传易感性和环境应激因素的特定组合，从而在受影响的脆弱神经元中引发与年龄相关的应激和蛋白稳态功能障碍。对脉管系统，免疫系统和局部神经胶质细胞的损害会介导环境压力，这可能会在各个阶段引发疾病。

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