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首页> 外文期刊>Expert opinion on therapeutic targets >The road to LOAD: late-onset Alzheimer's disease and a possible way to block it.
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The road to LOAD: late-onset Alzheimer's disease and a possible way to block it.

机译：负载之路：晚期阿尔茨海默氏病和可能的阻止它的方法。

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The ageing brain becomes increasingly less able to destroy or eject toxic amyloid (A) beta42 peptide byproducts of normal neuronal activity that consequently accumulate to induce Alzheimer's disease (AD). Therefore, the various components of the Abeta-clearing machinery are prime targets for AD therapeutics. In this connection, there are reports that taking statins to lower circulating cholesterol to prevent cardiovascular disease can also prevent late-onset AD (LOAD) the most common form of the disease. However, it seems unlikely that statins would prevent LOAD by lowering the very long-lived brain cholesterol that is controlled independently from the very much shorter-lived circulating cholesterol. In fact, reducing the ability of the brain astrocytes to make cholesterol for their closely associated neuron clients' synaptogenesis could damage the brain rather than protect it. However, a plausible way statins might prevent LOAD is to target a main component of the clearance machinery, low-density lipoprotein receptor-related protein 1 (LRP1), the brain's powerful Abeta-efflux driver. This is indicated by a reported ability of micromolar concentrations of lovastatin and simvastatin to strongly stimulate brain vascular endothelial cells to make this Abeta ejector. Therefore, if this holds up, taking a statin over the years would prevent the normal decline of LRP1 in the ageing brain and a LOAD-driving accumulation of Abeta.
机译：衰老的大脑越来越无法破坏或排出正常神经元活性的有毒淀粉样蛋白（A）beta42肽副产物，从而积聚成诱发阿尔茨海默氏病（AD）。因此，Abeta清除机制的各种组件是AD治疗的主要目标。在这方面，有报道说服用他汀类药物降低循环胆固醇以预防心血管疾病也可以预防最常见的疾病晚期AD（LOAD）。但是，他汀类药物似乎不太可能通过降低寿命很长的脑胆固醇而降低负荷，而胆固醇是由寿命很短的循环胆固醇独立控制的。实际上，降低大脑星形胶质细胞为其密切相关的神经元客户的突触生成胆固醇的能力可能会损害大脑，而不是保护大脑。然而，他汀类药物可能阻止LOAD的一种可行方法是针对清除机制的主要成分，即低密度脂蛋白受体相关蛋白1（LRP1），这是大脑强大的Abeta外排驱动器。报道的微摩尔浓度的洛伐他汀和辛伐他汀具有强烈刺激脑血管内皮细胞以制造这种Abeta喷射器的能力，这表明了这一点。因此，如果这种情况持续下去，多年来服用他汀类药物将防止LRP1在衰老的大脑中正常下降以及LOAD驱动的Abeta积累。

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