(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants.
(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants.
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带电和不带电表面活性剂对 α-突触核蛋白纤维聚集的稳定性（去稳定性）。
DOI：
10.3390/ijms222212509
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发表时间：
2021-11-19
影响因子：
5.6
通讯作者：
Pereira MC
中科院分区：
文献类型：
--
作者：
Loureiro JA;Andrade S;Goderis L;Gomez-Gutierrez R;Soto C;Morales R;Pereira MC
帕金森病（PD）是第二常见的神经退行性疾病。PD的一个重要特征是在称为路易体的结构中蛋白质的病理聚集。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-片的构象。α-突触核蛋白的错误折叠、聚集和纤颤机制尚不清楚，但人们认为α-突触核蛋白的β-薄片构象是其相关毒性机制的原因。为了深入了解α-突触核蛋白的错误折叠和聚集过程，我们对α-突触核蛋白在带电和不带电表面活性剂溶液下的二级结构进行了表征。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（不带电）辛基β- d -葡萄糖吡喃苷（OG）。通过超结构分析、体外聚集分析和二级结构分析来评价表面活性剂对α-突触核蛋白错误折叠的影响。带负电荷的SDS存在时α-突触核蛋白聚集表明SDS单体配合物刺激了聚集过程。减少N端和c端之间的静电斥力以及NAC（非淀粉样蛋白成分）区域和c端之间的疏水相互作用似乎对进行聚集很重要。傅里叶变换红外光谱（FTIR）测量表明，β-薄片结构包括原纤维的组装。
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.
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影响因子：
2.1
作者：
Loureiro, Joana A.;Rocha, Sandra;Pereira, Maria do Carmo
通讯作者：
Pereira, Maria do Carmo
影响因子：
3.4
作者：
Ghiglieri V;Calabrese V;Calabresi P
通讯作者：
Calabresi P
DOI：
10.3390/molecules22020277
发表时间：
2017-02-13
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Loureiro JA;Andrade S;Duarte A;Neves AR;Queiroz JF;Nunes C;Sevin E;Fenart L;Gosselet F;Coelho MA;Pereira MC
通讯作者：
Pereira MC
影响因子：
4.8
作者：
Necula, M;Chirita, CN;Kuret, J
通讯作者：
Kuret, J
DOI：
10.1016/s0014-827x(00)00083-5
发表时间：
2000-09-01
期刊：
FARMACO
影响因子：
--
作者：
Baquerizo, I;Ruiz, MA;Gallardo, V
通讯作者：
Gallardo, V