Munishkina L A, Fink A L, Uversky V N
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
Curr Alzheimer Res. 2009 Jun;6(3):252-60. doi: 10.2174/156720509788486491.
To better model the characteristics of crowded intracellular environments, we examined the effect of several factors known to induce partial folding and accelerated fibrillation of alpha-synuclein in dilute solutions, on the fibrillation of this protein in a crowded milieu. We found that low pH, certain metals and pesticides, polyanions, polycations and low concentrations of organic solvents cause a significant acceleration of alpha-synuclein fibrillation in the presence of high concentrations of polyethylene glycol. This suggests that the fibril-promoting effects of factors inducing partial folding of alpha-synuclein and the fibril-stimulating effects of macromolecular crowding are relatively independent and thus might act additively or even synergistically.
为了更好地模拟拥挤的细胞内环境的特征，我们研究了几种已知在稀溶液中能诱导α-突触核蛋白部分折叠并加速其纤维化的因素，对该蛋白在拥挤环境中纤维化的影响。我们发现，在高浓度聚乙二醇存在的情况下，低pH值、某些金属和农药、聚阴离子、聚阳离子以及低浓度有机溶剂会显著加速α-突触核蛋白的纤维化。这表明诱导α-突触核蛋白部分折叠的因素的促纤维作用与大分子拥挤的促纤维作用相对独立，因此可能具有累加甚至协同作用。
