Neurodegenerative disease - Amyloid pores from pathogenic mutations
Neurodegenerative disease - Amyloid pores from pathogenic mutations
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DOI：
10.1038/418291a
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发表时间：
2002-07-18
期刊：
影响因子：
64.8
通讯作者：
Lansbury, PT
中科院分区：
文献类型：
--
作者：
Lashuel, HA;Hartley, D;Lansbury, PT
阿尔茨海默病和帕金森病分别与脑中由β-淀粉样蛋白和α-突触核蛋白形成淀粉样纤维有关。可能是低聚纤维化中间体（原纤维），而不是原纤维本身，是致病的，但它们引起神经元死亡的机制仍然是一个谜。我们在这里表明，与家族性阿尔茨海默氏症和帕金森氏症相关的突变淀粉样蛋白形成形态学上难以区分的环状原纤维，类似于一类成孔细菌毒素，这表明不适当的膜透化可能是淀粉样疾病中细胞功能障碍甚至细胞死亡的原因。
Alzheimer's and Parkinson's diseases are associated with the formation in the brain of amyloid fibrils from β-amyloid and α-synuclein proteins, respectively. It is likely that oligomeric fibrillization intermediates (protofibrils), rather than the fibrils themselves, are pathogenic, but the mechanism by which they cause neuronal death remains a mystery. We show here that mutant amyloid proteins associated with familial Alzheimer's and Parkinson's diseases form morphologically indistinguishable annular protofibrils that resemble a class of pore-forming bacterial toxins, suggesting that inappropriate membrane permeabilization might be the cause of cell dysfunction and even cell death in amyloid diseases.