N-α-乙酰化是真核蛋白质中经常发生的翻译后修饰。它对几种蛋白质的调节和功能具有多种生理作用,新兴研究表明,它是压力反应的全球调节器。几十年来,使用非乙酰化αS进行了体外生化研究,以了解内在无序蛋白α-突触核蛋白(αS)在帕金森病(PD)病因学中的确切作用.α-突触核蛋白的N端现在明确已知在体内被乙酰化,然而,翻译后修饰的许多方面尚未得到很好的理解。αS的N-α-乙酰化是类似于大多数细胞蛋白的组成型修饰,还是时空调节?αS的N-α-乙酰化与αS的功能有关吗?αS的N-α-乙酰化如何影响αS向淀粉样蛋白的聚集?这里,我们概述了当前的知识,并讨论了关于αS的N-α-乙酰化对其构象的影响的普遍假设,寡聚,和纤维状态。αS的N-α-乙酰化程度对其功能至关重要,膜结合,和聚集成淀粉样蛋白也在这里探索。我们进一步讨论了αS的N-α-乙酰化在路易体形成和突触核蛋白病中的功能和致病意义。
N-α-acetylation is a frequently occurring post-translational modification in eukaryotic proteins. It has manifold physiological consequences on the regulation and function of several proteins, with emerging studies suggesting that it is a global regulator of stress responses. For decades, in vitro biochemical investigations into the precise role of the intrinsically disordered protein alpha-synuclein (αS) in the etiology of Parkinson\'s disease (PD) were performed using non-acetylated αS. The N-terminus of α-synuclein is now unequivocally known to be acetylated in vivo, however, there are many aspects of this post-translational modifications that are not understood well. Is N-α-acetylation of αS a constitutive modification akin to most cellular proteins, or is it spatio-temporally regulated? Is N-α-acetylation of αS relevant to the as yet elusive function of αS? How does the N-α-acetylation of αS influence the aggregation of αS into amyloids? Here, we provide an overview of the current knowledge and discuss prevailing hypotheses on the impact of N-α-acetylation of αS on its conformational, oligomeric, and fibrillar states. The extent to which N-α-acetylation of αS is vital for its function, membrane binding, and aggregation into amyloids is also explored here. We further discuss the overall significance of N-α-acetylation of αS for its functional and pathogenic implications in Lewy body formation and synucleinopathies.