Early-life events may trigger biochemical pathways for Alzheimer's disease: the "LEARn" model.
Early-life events may trigger biochemical pathways for Alzheimer's disease: the "LEARn" model.
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DOI：
10.1007/s10522-008-9162-6
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发表时间：
2008-12
期刊：
影响因子：
4.5
通讯作者：
Maloney B
中科院分区：
文献类型：
--
作者：
Lahiri DK;Zawia NH;Greig NH;Sambamurti K;Maloney B
阿尔茨海默病 (AD) 是老年人中最常见的痴呆症，大多在成年晚期出现。然而，目前尚不清楚疾病过程何时开始以及病理生化过程需要多长时间才能发展。我们的目标是解决导致 AD 的触发因素的时间和性质。为了解释 AD 的病因，我们最近提出了“潜在早期相关调节”（LEARn）模型，该模型假设在发育阶段触发特定基因的潜在表达。该模型整合了与疾病相关的神经病理学特征（例如，淀粉样蛋白斑块和 tau 蛋白缠结）和环境因素（例如饮食、金属暴露和激素）。环境因素从早期发育阶段开始以长期方式扰乱基因调控，但这些扰动直到生命后期才会产生病理结果。 LEARn 模型通过基因的调控区（启动子）并影响特定基因启动子内的甲基化状态来运作。
Alzheimer's disease (AD), the most common form of dementia among the elderly, manifests mostly late in adult life. However, it is presently unclear when the disease process starts and how long the pathobiochemical processes take to develop. Our goal is to address the timing and nature of triggers that lead to AD. To explain the etiology of AD, we have recently proposed a “Latent Early Associated Regulation” (LEARn) model, which postulates a latent expression of specific genes triggered at the developmental stage. This model integrates both the neuropathological features (e.g., amyloid-loaded plaques and tau-laden tangles) and environmental factors (e.g., diet, metal exposure, and hormones) associated with the disease. Environmental agents perturb gene regulation in a long-term fashion, beginning at early developmental stages, but these perturbations do not have pathological results until significantly later in life. The LEARn model operates through the regulatory region (promoter) of the gene and by affecting the methylation status within the promoter of specific genes.