免疫蛋白酶体PSMB8的上调与帕金森病相关。

Upregulation of immunoproteasome PSMB8 is associated with Parkinson's disease.

作者信息

Nguyen Huu Dat, Kim Young Eun, Nhat Nguyen Linh Thi, Kwak In Hee, Lee Yoon Kyoung, Kim Yun Joong, Hai Nguyen Thanh Thi, Pham Hong Ngoc, Ma Hyeo-Il

机构信息

Department of Medical Sciences, Graduate School of Hallym University, Chuncheon, Gangwon, 24252, South Korea; Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University, Anyang, Gyeonggi, 14068, South Korea.

Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University, Anyang, Gyeonggi, 14068, South Korea; Hallym Neurological Institute, Hallym University, Anyang, Gyeonggi, 14068, South Korea.

出版信息

Parkinsonism Relat Disord. 2023 Sep;114:105797. doi: 10.1016/j.parkreldis.2023.105797. Epub 2023 Aug 5.

DOI:10.1016/j.parkreldis.2023.105797

PMID:37562243

Abstract

BACKGROUND

Immunoproteasome, a part of ubiquitin-proteasome system, is involved in immune response as well as protein degradation. However, the relationship between immunoproteasome and Parkinson's disease (PD) was not evaluated clearly. We hypothesized that the shift of immunoproteasome attributes to PD pathogenesis due to its role in inflammation and protein homeostasis.

OBJECTIVE

To determine whether immunoproteasome in peripheral blood mononuclear cells (PBMC) and brain is expressed differently between patients with PD and healthy controls (HC).

METHODS

Blood samples were collected from 19 HC to 40 patients with PD of comparable ages. Peripheral blood mononuclear cells were isolated and followed by RT-qPCR to measure the mRNA levels of three catalytic subunits of immunoproteasome, namely, PSMB8, PSMB9, and PSMB10. Then, the protein levels of each subunit were measured by western blot. Finally, we confirmed the altered immunoproteasome subunit in the post-mortem human brain of PD.

RESULTS

In PBMCs, PSMB8 mRNA expression of PD group significantly increased compared to HC (p = 0.004), whereas PSMB9 and PSMB10 mRNA were not different between the PD and HC. The ratio of PSMB10 and PSMB8 mRNA (PSMB10/8 ratio) also reflected the significant difference between the PD and HC (p = 0.002). The PSMB10/8 ratio was well correlated with the UPDRS total and Part III score in the early stage of PD (Hoehn and Yahr ≤2.5) or drug-naïve PD subgroups. In terms of the protein level of immunoproteasome subunits in PBMCs, the increase of PSMB8 protein was observed in PD compared to HC (p = 0.0009), while PSMB9 and PSMB10 were not different between groups. Finally, we confirmed that immunoproteasome PSMB8 was expressed abundantly in the postmortem PD brain compared with normal control.

CONCLUSION

Our novel findings implicate that immunoproteasome PSMB8 is engaged in PD pathomechanism.

摘要

背景

免疫蛋白酶体作为泛素 - 蛋白酶体系统的一部分，参与免疫反应以及蛋白质降解。然而，免疫蛋白酶体与帕金森病（PD）之间的关系尚未得到明确评估。我们推测，免疫蛋白酶体因其在炎症和蛋白质稳态中的作用而在PD发病机制中具有重要作用。

目的

确定外周血单核细胞（PBMC）和脑中的免疫蛋白酶体在PD患者和健康对照（HC）之间的表达是否存在差异。

方法

收集了19名年龄相仿的HC和40名PD患者的血样。分离外周血单核细胞，然后通过RT-qPCR测量免疫蛋白酶体的三个催化亚基，即PSMB8、PSMB9和PSMB10的mRNA水平。随后，通过蛋白质印迹法测量每个亚基的蛋白质水平。最后，我们在PD患者的尸检人脑样本中证实了免疫蛋白酶体亚基的改变。

结果

在PBMC中，与HC相比，PD组的PSMB8 mRNA表达显著增加（p = 0.004），而PSMB9和PSMB10 mRNA在PD组和HC组之间没有差异。PSMB10与PSMB8 mRNA的比值（PSMB10/8比值）也反映了PD组和HC组之间的显著差异（p = 0.002）。PSMB10/8比值与PD早期（Hoehn和Yahr≤2.5）或未服用药物的PD亚组中的UPDRS总分和第三部分评分密切相关。就PBMC中免疫蛋白酶体亚基的蛋白质水平而言，与HC相比，PD组中观察到PSMB8蛋白增加（p = 0.0009），而PSMB9和PSMB10在两组之间没有差异。最后，我们证实与正常对照相比，免疫蛋白酶体PSMB8在PD患者的尸检脑中大量表达。