Cellular polyamines promote the aggregation of α-synuclein
Cellular polyamines promote the aggregation of α-synuclein
复制标题
DOI：
10.1074/jbc.m208249200
复制
发表时间：
2003-01-31
影响因子：
4.8
通讯作者：
Subramaniam, V
中科院分区：
文献类型：
--
作者：
Antony, T;Hoyer, W;Subramaniam, V
细胞内的多胺腐胺、亚精胺和精胺加速α-突触核蛋白的聚集和固定，α-突触核蛋白是与帕金森病相关的路易体的主要蛋白质成分。圆二色谱和荧光硫磺素T动力学研究表明，α-突触核蛋白的过渡从未聚集到高度聚集的状态，其特征在于滞后和过渡阶段。在多胺的存在下，滞后和过渡时间显着缩短。所有这三种多胺加速α-突触核蛋白的聚集和fifilization的程度增加的总电荷，长度和浓度的多胺。滞后期后的反应产物的电子和扫描力显微镜显示聚集颗粒（原纤维）和小纤维的存在。在过渡阶段结束时，α-突触核蛋白在所有情况下形成长纤维，尽管一些形态学变化是明显的。在多胺的存在下，原纤维形成大的网络，最终导致凝聚的聚集体。在不存在多胺的情况下，原纤维大多是孤立的。我们的结论是，在生理浓度的多胺可以调节α-突触核蛋白形成原纤维的倾向，因此可能发挥作用，在形成胞质α-突触核蛋白聚集体。
The cellular polyamines putrescine, spermidine, and spermine accelerate the aggregation and fibrillization of alpha-synuclein, the major protein component of Lewy bodies associated with Parkinson's disease. Circular dichroism and fluorometric thioflavin T kinetic studies showed a transition of alpha-synuclein from unaggregated to highly aggregated states, characterized by lag and transition phases. In the presence of polyamines, both the lag and transition times were significantly shorter. All three polyamines accelerated the aggregation and fibrillization of alpha-synuclein to a degree that increased with the total charge, length, and concentration of the polyamine. Electron and scanning force microscopy of the reaction products after the lag phase revealed the presence of aggregated particles (protofibrils) and small fibrils. At the end of the transition phase, alpha-synuclein formed long fibrils in all cases, although some morphological variations were apparent. In the presence of polyamines, fibrils formed large networks leading ultimately to condensed aggregates. In the absence of polyamines, fibrils were mostly isolated. We conclude that the polyamines at physiological concentrations can modulate the propensity of alpha-synuclein to form fibrils and may hence play a role in the formation of cytosolic alpha-synuclein aggregates.