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首页> 外文期刊>Lancet Neurology >Epigenetics of dementia: understanding the disease as a transformation rather than a state
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Epigenetics of dementia: understanding the disease as a transformation rather than a state

机译：痴呆症的表观遗传学：将疾病理解为一种转变而非状态

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Alzheimer's disease and other idiopathic dementias are associated with epigenetic transformations. These transformations connect the environment and genes to pathogenesis, and have led to the investigation of epigenetic-based therapeutic targes for the treatment of these diseases. Epigenetic changes occur over time in response to environmental effects. The epigenome-based latent early-life associated regulation (LEARn) hypothetical model indicates that accumulated environmental hits produce latent epigenetic changes. These hits can alter biochemical pathways until a pathological threshold is reached, which appears clinically as the onset of dementia. The hypotheses posed by LEARn are testable via longitudinal epigenome-wide, envirome-wide, and exposome-wide association studies (LEWAS) of the genome, epigenome, and environment. We posit that the LEWAS design could lead to effective prevention and treatments by identifying potential therapeutic strategies. Epigenetic evidence suggests that dementia is not a suddenly occurring and sharply delineated state, but rather a gradual change in crucial cellular pathways, that transforms an otherwise healthy state, as a result of neurodegeneration, to a dysfunctional state. Evidence from epigenetics could lead to ways to detect, prevent, and reverse such processes before clinical dementia.
机译：阿尔茨海默氏病和其他特发性痴呆与表观遗传转化有关。这些转化将环境和基因与发病机制联系起来，并导致对基于表观遗传学的治疗靶标进行研究，以治疗这些疾病。表观遗传变化随时间而发生，以响应环境影响。基于表观基因组的潜在早期生命相关调节（LEARn）假设模型表明，累积的环境影响产生了潜在的表观遗传变化。这些命中可以改变生化途径，直到达到病理学阈值为止，该阈值在临床上表现为痴呆症的发作。 LEARn提出的假设可通过基因组，表观基因组和环境的纵向表观基因组范围，整个环境组和暴露体范围的关联研究（LEWAS）进行检验。我们认为LEWAS设计可以通过确定潜在的治疗策略来导致有效的预防和治疗。表观遗传学证据表明，痴呆不是突然发生且轮廓分明的状态，而是关键细胞途径的逐渐变化，其由于神经变性而将原本健康的状态转变为功能障碍状态。表观遗传学的证据可能导致在痴呆之前检测，预防和逆转此类过程的方法。

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