El-Agnaf O M, Jakes R, Curran M D, Middleton D, Ingenito R, Bianchi E, Pessi A, Neill D, Wallace A
Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University Belfast, UK.
FEBS Lett. 1998 Nov 27;440(1-2):71-5. doi: 10.1016/s0014-5793(98)01418-5.
Alpha-synuclein (alpha-syn) protein and a fragment of it, called NAC, 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.
α-突触核蛋白（α-syn）及其一个名为NAC的片段已被发现与多种神经退行性疾病的病理损伤有关。最近，在易患遗传性帕金森病的家族中报道了α-syn基因的突变。我们已经表明，人类野生型α-syn、突变型α-syn（Ala30Pro）和突变型α-syn（Ala53Thr）蛋白能够自我聚集并形成淀粉样细丝。在此我们报告，NAC和α-syn蛋白的聚集体可诱导人神经母细胞瘤SH-SY5Y细胞发生凋亡性细胞死亡。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发病机制的发展中起主要作用。
