A new hypothesis of neurodegenerative diseases: the deleterious network hypothesis.

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.