Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.
Int J Biol Macromol. 2021 Apr 30;177:392-400. doi: 10.1016/j.ijbiomac.2021.02.150. Epub 2021 Feb 22.
We have been investigating the early stages of α-synuclein (Syn) aggregation, a small presynaptic protein implicated in Parkinson's disease. We previously reported that for pH jumps (1000 s) from pH 7 to pH 2 the variation of the Syn intrinsic fluorescence intensity did not change in the concentration range of ca. 10-50 μM (ref. 16). Additionally, I reported dynamic light scattering (DLS) experiments revealing the formation of early large Syn aggregates (ref. 7). These reported results mean that some molecular entity is being early formed. Herein, it was decided to investigate in detail these early Syn aggregates by using light scattering. By DLS analysis, these aggregates exhibited a hydrodynamic diameter of ca. 420 nm along with a high scattering intensity, characteristic of micellar-like aggregates formation. The critical micelle concentration (CMC) at which the Syn micellar-like aggregates are formed was ca. 10 μM. DLS analysis has also revealed that the micellar-like aggregates for Syn evolved, for protein concentrations >100 μM, to the formation of smaller aggregates (hydrodynamic diameter of ca. 165 nm), possibly Syn oligomers. The Syn micellar-like aggregates formed at pH 7 solutions seem to be active species and to have a role in this protein aggregation mechanism.
我们一直在研究α-突触核蛋白（Syn）聚集的早期阶段，这是一种与帕金森病有关的小突触前蛋白。我们之前报道过，对于 pH 从 7 跃变到 2 的情况（1000 秒），在约 10-50μM 的浓度范围内，Syn 固有荧光强度的变化没有改变（参考文献 16）。此外，我还报告了动态光散射（DLS）实验，揭示了早期大 Syn 聚集体的形成（参考文献 7）。这些报道的结果意味着一些分子实体正在早期形成。在此，我们决定通过使用光散射详细研究这些早期的 Syn 聚集体。通过 DLS 分析，这些聚集体表现出约 420nm 的流体力学直径，以及高散射强度，这是形成胶束样聚集体的特征。Syn 胶束样聚集体形成的临界胶束浓度（CMC）约为 10μM。DLS 分析还表明，对于蛋白质浓度大于 100μM 的 Syn，胶束样聚集体演变成更小的聚集体（约 165nm 的流体力学直径），可能是 Syn 低聚物。在 pH 7 溶液中形成的 Syn 胶束样聚集体似乎是活性物质，并且在这种蛋白质聚集机制中具有作用。
