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Circular RNAs in Parkinson’s Disease: Reliable Biological Markers and Targets for Rehabilitation

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Abstract

In clinical practice, the underlying pathogenesis of Parkinson’s disease (PD) remains unknown. Circular RNAs (circRNAs) have good biological properties and can be used as biological marker. Rehabilitation as a third treatment alongside drug and surgery has been shown to be clinically effective, but biomarkers of rehabilitation efficiency at genetic level is still lacking. In this study, we identified differentially expressed circRNAs in peripheral blood exosomes between PD patients and health controls (HCs) and determined whether these circRNAs changed after rehabilitation, to explore the competing RNA networks and epigenetic mechanisms affected. We found that there were 558 upregulated and 609 downregulated circRNAs in PD patients compared to HCs, 3398 upregulated and 479 downregulated circRNAs in PD patients after rehabilitation compared to them before rehabilitation, along with 3721 upregulated and 635 downregulated circRNAs in PD patients after rehabilitation compared to HCs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially expressed circRNAs may affect the stability of the cellular actin backbone and synaptic structure by influencing the aggregation of α-synuclein (a-syn). We selected two circRNAs overexpressed in PD patients for validation (hsa_circ_0001535 and hsa_circ_0000437); the results revealed that their expression levels were all reduced to varying degrees (p < 0.05) after rehabilitation. After network analysis, we believe that hsa_circ_0001535 may be related to the aggregation of a-syn, while hsa_circ_0000437 may act on hsa-let-7b-5p or hsa-let-7c-5p through sponge effect to cause inflammatory response. Our findings suggest that rehabilitation can mitigate the pathological process of PD by epigenetic means.

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Data Availability

The datasets generated during and/or analyzed during the current study are available in the online repository, https://ngdc.cncb.ac. cn/gsa-human/, HRA002383.

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Acknowledgements

The authors wish to thank Pro.BF for her constant guidance through all the stages of the writing of this manuscript.

Funding

This work was supported by the Science and Technology Development Fund of Beijing Rehabilitation Hospital, Capital Medical University (2019–023 to YL, 2020–069, 2021–011 to BF, and 2020R-001 to YW).

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  1. Yinan Duan and Yixuan Wang have contributed equally to this work.

Authors and Affiliations

  1. Capital Medical University School of Beijing Rehabilitation Medicine, Capital Medical University, Beijing, China

    Yinan Duan, Xin Yu & Keke Chen

  2. Parkinson Medical Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China

    Yixuan Wang, Yonghong Liu, Zhaohui Jin, Cui Liu, Detao Meng, Jianing Xi & Boyan Fang

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Contributions

JX and BF contributed to the study conception and design. Material preparation and data collection were performed by YL, ZJ, CL, XY, KC, and DM. Statistical analysis was performed by YD and YW. The first draft of the manuscript was written by YD, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jianing Xi or Boyan Fang.

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Duan, Y., Wang, Y., Liu, Y. et al. Circular RNAs in Parkinson’s Disease: Reliable Biological Markers and Targets for Rehabilitation. Mol Neurobiol 60, 3261–3276 (2023). https://doi.org/10.1007/s12035-023-03268-0

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