THE CORE ALZHEIMERS PEPTIDE NAC FORMS AMYLOID FIBRILS WHICH SEED AND ARE SEEDED BY BETA-AMYLOID - IS NAC A COMMON TRIGGER OR TARGET IN NEURODEGENERATIVE DISEASE
THE CORE ALZHEIMERS PEPTIDE NAC FORMS AMYLOID FIBRILS WHICH SEED AND ARE SEEDED BY BETA-AMYLOID - IS NAC A COMMON TRIGGER OR TARGET IN NEURODEGENERATIVE DISEASE
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DOI：
10.1016/1074-5521(95)90071-3
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发表时间：
1995-03-01
影响因子：
--
通讯作者：
LANSBURY, PT
中科院分区：
文献类型：
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作者：
HAN, HY;WEINREB, PH;LANSBURY, PT
背景：NAC是从阿尔茨海默病（AD）淀粉样斑块的不溶性核心中分离得到的一种35个氨基酸的肽。它是α-突触核蛋白（或NACP）的片段，一种功能未知的神经元蛋白。我们注意到一个惊人的序列之间的相似性NAC，β-淀粉样蛋白的羧基末端，和一个区域的痒病朊病毒蛋白（PrP）已牵连在淀粉样蛋白formation.Results：NAC的制备通过化学合成，并被发现通过成核依赖的聚合机制形成淀粉样纤维。NAC淀粉样蛋白纤维有效地播种β 1-40淀粉样蛋白形成。淀粉样蛋白原纤维包括肽模型的同源β和PrP序列也被发现种子淀粉样蛋白形成NAC.Conclusions：在体外模型研究表明，播种NAC淀粉样蛋白形成的β-淀粉样蛋白，或播种的β-淀粉样蛋白的淀粉样蛋白原纤维的NAC，可能会发生体内。有序NAC聚集体在突触中的积累可能是AD和朊病毒疾病中观察到的神经变性的原因。或者，神经变性可能是由α-突触核蛋白（NACP）功能丧失引起的。
Background: NAC is a 35-amino-acid peptide which has been isolated from the insoluble core of Alzheimer's disease (AD) amyloid plaque. It is a fragment of alpha-synuclein (or NACP), a neuronal protein of unknown function. We noted a striking sequence similarity between NAC, the carboxyl terminus of the beta-amyloid protein, and a region of the scrapie prion protein (PrP) which has been implicated in amyloid formation.Results: NAC was prepared by chemical synthesis and was found to form amyloid fibrils via a nucleation-dependent polymerization mechanism. NAC amyloid fibrils effectively seed beta 1-40 amyloid formation. Amyloid fibrils comprising peptide models of the homologous beta and PrP sequences were also found to seed amyloid formation by NAC.Conclusions: The in vitro model studies presented here suggest that seeding of NAC amyloid formation by the beta-amyloid protein, or seeding of amyloid fibrils of the beta-amyloid protein by NAC, may occur invivo. Accumulation of ordered NAC aggregates in the synapse may be responsible for the neurodegeneration observed in AD and the prion disorders. Alternatively, neurodegeneration may be caused by the loss of alpha-synuclein (NACP) function.