LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, 4200-465 Porto, Portugal.
Faculty of Pharmaceutical Sciences, Ghent University, Sint-Pietersnieuwstraat 25, B-9000 Ghent, Belgium.
Int J Mol Sci. 2021 Nov 19;22(22):12509. doi: 10.3390/ijms222212509.
Parkinson's disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-synuclein can assume conformations rich in either α-helix or β-sheets. The mechanisms of α-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that β-sheet conformation of α-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of α-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl β-D-glucopyranoside (OG). The effect of surfactants in α-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The α-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that β-sheet structures comprise the assembly of the fibrils.
帕金森病（PD）是第二常见的神经退行性疾病。PD 的一个重要标志涉及到称为路易体的结构中蛋白质的病理性聚集。这些蛋白包涵体的主要成分是α（α）-突触核蛋白。在不同的条件下，α-突触核蛋白可以呈现富含α-螺旋或β-折叠的构象。α-突触核蛋白错误折叠、聚集和纤维化的机制尚不清楚，但人们认为α-突触核蛋白的β-折叠构象与其相关的毒性机制有关。为了深入了解α-突触核蛋白错误折叠和聚集的过程，研究了在带电荷和不带电荷的表面活性剂溶液中该蛋白质的二级结构。选择的表面活性剂为（阴离子）十二烷基硫酸钠（SDS）、（阳离子）十六烷基三甲基氯化铵（CTAC）和（非离子）辛基-β-D-吡喃葡萄糖苷（OG）。通过超微结构分析、体外聚集测定和二级结构分析评估了表面活性剂对α-突触核蛋白错误折叠的影响。带负电荷的 SDS 存在下的α-突触核蛋白聚集表明 SDS-单体复合物刺激了聚集过程。似乎重要的是，N-和 C-末端之间的静电排斥减少以及 NAC（非淀粉样β成分）区域和 C-末端之间的疏水性相互作用减少，以进行聚集。傅里叶变换红外光谱（FTIR）测量表明β-折叠结构构成了纤维的组装。
