Expert Opin Ther Targets. 2012 Apr;16(4):351-4. doi: 10.1517/14728222.2012.664135. Epub 2012 Feb 18.
Neurodegenerative disease such as Alzheimer's, Parkinson and Huntington's are all characterized by dysfunctional neurons and loss of cognitive/motor functions. Interestingly these three diseases involve overproduction, aggregation or abnormal degradation of a specific aberrant protein, which participates in disease pathogenesis. The aggregated proteins may induce disease causing pathways such as high oxidative stress and reduced neuronal metabolism. Several mechanisms are being considered as disease-causing and there is established and growing evidence that a breakdown in neuronal energy production may be an underlying cause in these diseases. The specific risk factors and molecular drivers for each disease vary, yet there are common defective bioenergetics pathways, which may drive neuronal dysfunction. While it has been appreciated that energy deficits can drive neuronal dysfunction and disease, it has for the most part been overlooked as a target pathway for designing novel disease modifying therapeutics. This editorial reviews selected evidence supporting energy deficits as disease-causing and proposes targets for design of new therapeutics.
神经退行性疾病，如阿尔茨海默病、帕金森病和亨廷顿病，其特征都是神经元功能失调和认知/运动功能丧失。有趣的是，这三种疾病都涉及特定异常蛋白的过度产生、聚集或异常降解，而这些蛋白参与了疾病的发病机制。聚集的蛋白可能会诱导疾病发病途径，如氧化应激增加和神经元代谢减少。有几种机制被认为是致病的，并且有明确的、不断增加的证据表明，神经元能量产生的崩溃可能是这些疾病的潜在原因。每种疾病的具体风险因素和分子驱动因素都不同，但存在共同的、有缺陷的生物能量途径，这些途径可能会导致神经元功能障碍。尽管人们已经认识到能量不足会导致神经元功能障碍和疾病，但在很大程度上，它被忽视了作为设计新型疾病修饰治疗的靶向途径。本社论综述了支持能量不足作为致病因素的选定证据，并提出了设计新型治疗药物的靶点。
