Ying W
School of Medicine, University of New Mexico, Albuquerque 87131, USA.
Med Hypotheses. 1996 Oct;47(4):307-13. doi: 10.1016/s0306-9877(96)90071-7.
Growing evidence has indicated the existence of deleterious networks in the brains of neurodegenerative disorders, including Alzheimer's disease. Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. The deleterious networks are formed on the basis of the intimate interactions among the key pathogenic factors, including oxidative damage, aberrant calcium homeostasis, metabolic compromise and, under certain circumstances, amyloid precursor protein mismetabolism. Based on the novel concept, deleterious network, a unifying hypothesis, the deleterious network hypothesis of neurodegenerative diseases, is proposed. This new theory stresses that the deleterious network is just the common pathway of the degenerative disorders, triggering of which by aging, certain genetic or environmental factors leads to a cascade of pathological alterations of the illnesses. It appears that this new theory has synthesized some most appealing hypotheses about neurodegenerative illnesses, providing consistent explanations to a larger number of observations about those diseases than other hypotheses. Because the disorders appear to result from the interactions among the key detrimental factors, it is suggested that the patients of the neurodegenerative diseases should be treated by combinative application of the drugs which can diminish peroxidative damage, calcium mismetabolism, and metabolic compromise.
越来越多的证据表明，在包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿舞蹈症在内的神经退行性疾病患者大脑中存在有害网络。这些有害网络是在关键致病因素之间密切相互作用的基础上形成的，这些因素包括氧化损伤、异常的钙稳态、代谢紊乱，以及在某些情况下淀粉样前体蛋白代谢异常。基于“有害网络”这一新概念，提出了一个统一的假说——神经退行性疾病的有害网络假说。这一新理论强调，有害网络正是这些退行性疾病的共同途径，衰老、某些遗传或环境因素触发该网络会导致一系列疾病的病理改变。看起来这一新理论综合了一些关于神经退行性疾病的极具吸引力的假说，相较于其他假说，它能对更多关于这些疾病的观察结果给出一致的解释。由于这些疾病似乎是由关键有害因素之间的相互作用导致的，因此有人建议，神经退行性疾病患者应采用联合应用能够减少过氧化损伤、钙代谢异常和代谢紊乱的药物进行治疗。
