Parkinson’s Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Recruitment of Parkinson’s Disease Patients and Healthy Controls
2.3. Blood Processing and Generation of Dopaminergic Neurons Derived from Induced Pluripotent Stem Cells
2.4. Cell Culture and Neuronal Differentiation
2.5. Immunofluorescence
2.6. STIP1-Derived Peptide Library
2.7. Production of Full-Length STIP1 Protein
2.8. Primary Hippocampal Neuronal Cell Culture
2.9. Peptide/Protein-Based ELISA
2.10. Cell Death Assay
2.11. T Cell ELISpot
2.12. Cancer Outlier Profile Analysis (COPA)
2.13. Statistical Analysis
3. Results
3.1. STIP1 Ameliorates Staurosporine-Induced Neurotoxicity on Dopaminergic Neurons Derived from hiPSC
3.2. STIP1-Specific Autoantibodies in Parkinson’s Disease Patients and Healthy Controls
3.3. STIP1-Specific T Cell Epitopes Cluster around the PrPC Binding Site
3.4. STIP1 Autoantibody Binding Sites Overlap with the HSP70 and PrPC Association Regions
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Parameters | Healthy Controls | Parkinson’s Disease Patients |
---|---|---|
Age (mean ± standard deviation) | 63.1 (±8) | 62.94 (±8.48) |
Gender (Sample size) | Males, n = 27 Females, n = 23 | Males, n = 27 Females, n = 23 |
Hoehn and Yahr Staging (%) | Not applicable | ≤2 (45%) >2 (55%) |
Ethnicity (Sample size) | Chinese, n = 50 | Chinese, n = 48 Eurasian, n = 1 Indian, n = 1 |
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Tan, J.S.Y.; Lee, B.; Lim, J.; Ma, D.R.; Goh, J.X.; Goh, S.Y.; Gulam, M.Y.; Koh, S.M.; Lee, W.W.; Feng, L.; et al. Parkinson’s Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1. Cells 2022, 11, 1649. https://doi.org/10.3390/cells11101649
Tan JSY, Lee B, Lim J, Ma DR, Goh JX, Goh SY, Gulam MY, Koh SM, Lee WW, Feng L, et al. Parkinson’s Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1. Cells. 2022; 11(10):1649. https://doi.org/10.3390/cells11101649
Chicago/Turabian StyleTan, Jolene Su Yi, Bernett Lee, Jackwee Lim, Dong Rui Ma, Jia Xin Goh, Suh Yee Goh, Muhammad Yaaseen Gulam, Ser Mei Koh, Weiling Wendy Lee, Lei Feng, and et al. 2022. "Parkinson’s Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1" Cells 11, no. 10: 1649. https://doi.org/10.3390/cells11101649