Kang Seo-Jun, Kim Jin Soo, Park Sang Myun
Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea.
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.
Exp Neurobiol. 2018 Oct;27(5):377-386. doi: 10.5607/en.2018.27.5.377. Epub 2018 Oct 31.
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons, and gathering evidence indicates that UCH-L1 may play pathogenic roles in many neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease (PD). Additionally, lipid rafts have attracted interest in neurodegeneration as playing a common role in many neurodegenerative diseases. In the present study, we demonstrated that UCH-L1 associates with lipid rafts as with other PD-associated gene products. In addition, UCH-L1 regulates lipid raft-dependent endocytosis and it is not dependent on the expression and degradation of caveolin-1 or flotillin-1. Finally, UCH-L1 regulates cell-to-cell transmission of α-synuclein. This study provides evidence that many PD-associated gene products share common signaling pathways to explain the pathogenesis of PD.
泛素羧基末端水解酶L1（UCH-L1）是一种去泛素化酶，在神经元中高度表达，越来越多的证据表明UCH-L1可能在许多神经退行性疾病如阿尔茨海默病和帕金森病（PD）中发挥致病作用。此外，脂筏在许多神经退行性疾病中发挥共同作用，因而在神经退行性变方面引起了关注。在本研究中，我们证明UCH-L1与脂筏相关联，如同与其他帕金森病相关基因产物一样。此外，UCH-L1调节脂筏依赖性内吞作用，且不依赖于小窝蛋白-1或小窝形成蛋白-1的表达和降解。最后，UCH-L1调节α-突触核蛋白的细胞间传递。这项研究提供了证据，表明许多帕金森病相关基因产物共享共同的信号通路来解释帕金森病的发病机制。
