Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio 7, 10257 Vilnius, Lithuania.
Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
Int J Mol Sci. 2021 Jul 26;22(15):7972. doi: 10.3390/ijms22157972.
The formation of amyloid fibril plaques in the brain creates inflammation and neuron death. This process is observed in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Alpha-synuclein is the main protein found in neuronal inclusions of patients who have suffered from Parkinson's disease. S100A9 is a calcium-binding, pro-inflammation protein, which is also found in such amyloid plaques. To understand the influence of S100A9 on the aggregation of α-synuclein, we analyzed their co-aggregation kinetics and the resulting amyloid fibril structure by Fourier-transform infrared spectroscopy and atomic force microscopy. We found that the presence of S100A9 alters the aggregation kinetics of α-synuclein and stabilizes the formation of a particular amyloid fibril structure. We also show that the solution's ionic strength influences the interplay between S100A9 and α-synuclein, stabilizing a different structure of α-synuclein fibrils.
在大脑中形成淀粉样纤维斑块会引发炎症和神经元死亡。这一过程在神经退行性疾病中很常见，如阿尔茨海默病和帕金森病。α-突触核蛋白是帕金森病患者神经元包含物中主要的蛋白质。S100A9 是一种钙结合的促炎蛋白，也存在于这种淀粉样斑块中。为了了解 S100A9 对 α-突触核蛋白聚集的影响，我们通过傅里叶变换红外光谱和原子力显微镜分析了它们的共聚集动力学和由此产生的淀粉样纤维结构。我们发现，S100A9 的存在改变了 α-突触核蛋白的聚集动力学，并稳定了特定淀粉样纤维结构的形成。我们还表明，溶液的离子强度会影响 S100A9 和 α-突触核蛋白之间的相互作用，从而稳定 α-突触核蛋白纤维的不同结构。
