α-突触核蛋白(α-syn)聚集在帕金森病(PD)的致病性中起关键作用。这项研究旨在评估使用人类和动物中发现的变异性设计的α-syn片段肽的聚集倾向。硫磺素T(ThT)和透射电子显微镜(TEM)用于验证原纤维的形成,以鉴定重要的氨基酸残基。与片段1-25、26-50和91-115相比,人α-syn片段51-75、37-61、62-86、76-100和116-140表现出明显更高的聚集趋势。分析的α-syn37-61和62-86区域的所有物种均显示在ThT和TEM上形成原纤维。α-syn37-61和62-86片段区域表现出对聚集的高度敏感性,在所有物种中观察到原纤维的形成。几个α-syn37-61片段中的A53T突变可能增强其聚集倾向,表明该突变与原纤维形成能力之间存在相关性。此外,非淀粉样β成分(NAC)区域的存在,特别是在α-syn62-86中,在几个显示原纤维形成的片段中一致观察到,表明NAC区域与α-syn中原纤维形成过程之间存在潜在的相关性。最后,这些片段中的大量缬氨酸和少量酸性氨基酸的组合可以用作α-syn原纤维形成的指示物。
Alpha-synuclein (α-syn) aggregation plays a critical role in the pathogenicity of Parkinson\'s Disease (PD). This study aims to evaluate the aggregation propensity of α-syn fragment peptides designed using the variability found in humans and animals. Thioflavin T (ThT) and transmission electron microscopy (TEM) were used to validate the formation of fibrils to identify important amino acid residues. Human α-syn fragments 51-75, 37-61, 62-86, 76-100, and 116-140 demonstrate a significantly higher tendency to aggregate compared to fragments 1-25, 26-50, and 91-115. All species analyzed of the α-syn 37-61 and 62-86 regions were shown to form fibrils on both ThT and TEM. The α-syn 37-61 and 62-86 fragment regions exhibited a high susceptibility to aggregation, with
fibril formation observed in all species. The A53T mutation in several α-syn 37-61 fragments may enhance their propensity for aggregation, suggesting a correlation between this mutation and the capacity for
fibril formation. Furthermore, the presence of the non-amyloid-β component (NAC) region, specifically in α-syn 62-86, was consistently observed in several fragments that displayed
fibril formation, indicating a potential correlation between the NAC region and the process of
fibril formation in α-syn. Finally, the combination of a high quantity of valine and a low quantity of acidic amino acids in these fragments may serve as indicators of α-syn
fibril formation.