Inactivation mechanism of alpha-synuclein oligomer toxicity in Parkinson's disease

在我们的研究中，我们研究神经元如何抵消α-突触核蛋白寡聚物在帕金森病中的有害影响。由于细胞中α-突触核蛋白水平过高，这些低聚物的积累与神经元死亡和疾病进展有关。我们的研究发现，溶酶体降解和聚合体的形成在阻止这些低聚物在神经元中的形成和中和毒性方面起着至关重要的作用。我们发现这些过程是由三种蛋白共同调控的：USP10， G3BP1和p62。我们发现USP10活性通过共享机制调节α-突触核蛋白的选择性降解，以及潜在的其他疾病相关蛋白。

In our study, we investigate how neurons counteract the harmful effects of toxic α-synuclein oligomers in Parkinson's disease. The accumulation of these oligomers, which occurs due to excessive α-synuclein levels in cells, is associated with neuronal death and disease progression. Our research has uncovered that lysosomal degradation and the formation of aggresomes play a crucial role in preventing the formation and neutralizing the toxicity of these oligomers in neurons. We identified that these processes are co-regulated by three proteins: USP10, G3BP1, and p62. We discovered USP10 activity to regulate selective degradation of α-synuclein, as well as potentially other disease-related proteins through shared mechanism.