Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai, India.
Biochemistry. 2014 Oct 21;53(41):6419-21. doi: 10.1021/bi5010365. Epub 2014 Oct 10.
α-Synuclein (α-Syn) oligomerization and amyloid formation are associated with Parkinson's disease (PD) pathogenesis. Studying familial α-Syn mutants associated with early onset PD has therapeutic importance. Here we report the aggregation kinetics and other biophysical properties of a newly discovered PD associated Finnish mutation (A53E). Our in vitro study demonstrated that A53E attenuated α-Syn aggregation and amyloid formation without altering the major secondary structure and initial oligomerization tendency. Further, A53E showed reduced membrane binding affinity compared to A53T and WT. The present study would help to delineate the role of A53E mutation in early onset PD pathogenesis.
α-突触核蛋白(α-Syn)寡聚化和淀粉样形成与帕金森病(PD)的发病机制有关。研究与早发性 PD 相关的家族性 α-Syn 突变体具有治疗意义。本文报告了一种新发现的与 PD 相关的芬兰突变(A53E)的聚集动力学和其他生物物理特性。我们的体外研究表明,A53E 减弱了 α-Syn 的聚集和淀粉样形成,而不改变主要的二级结构和初始寡聚化倾向。此外,与 A53T 和 WT 相比,A53E 显示出降低的膜结合亲和力。本研究将有助于阐明 A53E 突变在早发性 PD 发病机制中的作用。