Identification of BAG5 as a Potential Biomarker for Parkinson's Disease Patients With R492X PINK1 Mutation

Yu Fu; Yongkang Chen; Haiyan Tian; Han Liu; Dan Qi; Erxi Wu; Xuejing Wang

doi:10.3389/fnins.2022.903958

Identification of BAG5 as a Potential Biomarker for Parkinson's Disease Patients With R492X PINK1 Mutation

Front Neurosci. 2022 Jul 27:16:903958. doi: 10.3389/fnins.2022.903958. eCollection 2022.

Authors

Yu Fu^{1

2}, Yongkang Chen^{1

2}, Haiyan Tian^{1

2}, Han Liu^{1

2}, Dan Qi³, Erxi Wu^{3

4

5

6}, Xuejing Wang^{1

2}

Affiliations

¹ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Institute of Parkinson's Disease and Movement Disorders, Zhengzhou University, Zhengzhou, China.
³ Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, TX, United States.
⁴ Department of Surgery, Texas A&M University Health Science Center College of Medicine, Temple, TX, United States.
⁵ Department of Pharmaceutical Sciences, Texas A&M University Health Science Center, College of Pharmacy, College Station, TX, United States.
⁶ Livestrong Cancer Institutes, Dell Medical School, The University of Texas at Austin, Austin, TX, United States.

Abstract

Parkinson's disease (PD) is a degenerative, progressive nervous system disorder with an unknown cause. PINK1 [phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1] causative mutations R492X may cause autosomal recessive early-onset parkinsonism. In this study, we utilized patient samples and cell line system to investigate roles of Bcl2-associated athanogene 5 (BAG5) in PD patients with R492X PINK1 mutation. We show that the expression levels of BAG5 in the skin tissues from PD patients with R492X PINK1 mutation are markedly lower than those from the healthy control subjects in a small cohort of patients, which has not been recognized before. In addition, we demonstrate that BAG5 physically binds to R492X mutated PINK1 protein. Furthermore, we reveal that BAG5 promotes the degradation of R492X mutated PINK1 protein via ubiquitin/proteasome-dependent pathway, suggesting that decreased level of BAG5 may lead to R492X mutated PINK1 protein accumulation. These findings suggest that BAG5 may serve as an early detection biomarker for PD patients with R492X PINK1 mutation and provide important new insights on how BAG5 affects R492X mutated PINK1 protein, highlighting therapeutic targets for this disease.

Keywords: Bcl2-associated athanogene 5; Parkinson’s disease; R492X PINK1 mutation degradation; skin; ubiquitination.