Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments

Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments
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DOI:
10.1016/s0014-5793(98)01418-5
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发表时间:
1998-11-27
期刊:
影响因子:
3.5
通讯作者:
Wallace, A
Wallace, A
中科院分区:
生物学3区
文献类型:
--
作者:
El-Agnaf, OMA;Jakes, R;Wallace, A

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已经发现α-突触核蛋白(alpha-syn)蛋白及其片段(称为NAG)与许多神经退行性疾病的病理损害相关。最近,已经报道了在易患遗传形式的帕金森病的家族中α-syn基因的突变。我们已经证明,人类野生型α-syn,突变型α-syn(Ala 30 Pro)和突变型α-syn(Ala 53 Thr)蛋白可以自聚集并形成淀粉样纤维。在这里,我们报告NAC和α-syn蛋白的聚集体诱导人神经母细胞瘤SH-SY 5 Y细胞的凋亡性细胞死亡。这些发现表明,α-syn及其降解产物的积累可能在这些神经退行性疾病的发病机制的发展中发挥重要作用。(C)1998年欧洲生物化学学会联合会。
alpha-Synuclein (alpha-syn) protein and a fragment of it, called NAG, have been found in association with the pathological lesions of a number of neurodegenerative diseases, Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild-type alpha-syn, mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments, Here we report that aggregates of NAC and alpha-syn proteins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. These findings indicate that accumulation of alpha-syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases. (C) 1998 Federation of European Biochemical Societies.