Ying W
Department of Physiology, School of Medicine, University of New Mexico, Albuquerque 87131, USA.
Med Hypotheses. 1996 May;46(5):421-8. doi: 10.1016/s0306-9877(96)90021-3.
Numerous studies indicate that aberrant amyloid precursor protein metabolism, elevated peroxidative damage, depressed energy metabolism and altered calcium homeostasis are four pivotal deleterious factors in the pathogenesis of Alzheimer's disease. Cumulative evidence further suggests that these four factors are intimately interrelated, forming a deleterious network. Based on this new concept of 'deleterious network', a unifying hypothesis-the deleterious network hypothesis of Alzheimer's disease-is proposed. The main ideas of the hypothesis are delineated as follows: increases in free radical damage, alterations in amyloid precursor protein metabolism, impairment of energy metabolism and abnormalities of calcium homeostasis are four cornerstones of a deleterious network. Various risk factors of Alzheimer's disease can triger the network by promoting the occurrence of one of these key components, resulting in the biological abnormalities of Alzheimer's disease. Based on this new theory, a majority of the important observations about Alzheimer's disease can be explained consistently and succinctly.
大量研究表明，淀粉样前体蛋白代谢异常、过氧化损伤增加、能量代谢降低以及钙稳态改变是阿尔茨海默病发病机制中的四个关键有害因素。越来越多的证据进一步表明，这四个因素密切相关，形成一个有害网络。基于这种“有害网络”的新概念，提出了一个统一的假说——阿尔茨海默病的有害网络假说。该假说的主要观点如下：自由基损伤增加、淀粉样前体蛋白代谢改变、能量代谢受损以及钙稳态异常是有害网络的四大基石。阿尔茨海默病的各种危险因素可通过促进这些关键成分之一的发生来触发该网络，从而导致阿尔茨海默病的生物学异常。基于这一新理论，可以一致且简洁地解释关于阿尔茨海默病的大多数重要观察结果。
