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

帕金森病中α-突触核蛋白寡聚体毒性的灭活机制

• 批准号: 22K15377
• 负责人: アニシモフ セルゲイ
• 金额: $ 2.91万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K15377/
• 关键词: USP10; Synuclein; Neurodegeneration; Synucelin; G3BP1; Aggresome

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.

在我们的研究中，我们研究了神经元如何抵消帕金森病中有毒α-突触核蛋白寡聚体的有害影响。由于细胞中α-突触核蛋白水平过高而发生的这些寡聚体的蓄积与神经元死亡和疾病进展相关。我们的研究已经发现，溶酶体降解和攻击体的形成在防止这些寡聚体在神经元中的形成和中和毒性中起着至关重要的作用。我们发现这些过程由三种蛋白质共同调节：USP 10，G3 BP 1和p62。我们发现USP 10活性调节α-突触核蛋白的选择性降解，以及通过共享机制调节其他潜在的疾病相关蛋白。