Upregulation of immunoproteasome PSMB8 is associated with Parkinson's disease

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

doi:10.1016/j.parkreldis.2023.105797

Upregulation of immunoproteasome PSMB8 is associated with Parkinson's disease

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

Authors

Huu Dat Nguyen¹, Young Eun Kim², Linh Thi Nhat Nguyen¹, In Hee Kwak³, Yoon Kyoung Lee⁴, Yun Joong Kim⁵, Thanh Thi Hai Nguyen¹, Hong Ngoc Pham¹, Hyeo-Il Ma³

Affiliations

¹ 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.
² 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. Electronic address: yekneurology@hallym.ac.kr.
³ 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.
⁴ Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University, Anyang, Gyeonggi, 14068, South Korea.
⁵ Department of Neurology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi, South Korea.

PMID: 37562243
DOI: 10.1016/j.parkreldis.2023.105797

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.

Keywords: Immunoproteasome; PSMB8; Parkinson's disease; Peripheral blood mononuclear cells; Ubiquitin proteasome system.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Leukocytes, Mononuclear / metabolism
Parkinson Disease* / genetics
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism
RNA, Messenger
Up-Regulation

Substances

LMP7 protein
Proteasome Endopeptidase Complex
RNA, Messenger