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PreprintCited by 17Circular RNAs in diseasesParkinson's Disease Mechanisms and TreatmentsExtracellular vesicles in disease

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Circular RNAs in Parkinson’s Disease: Reliable Biological markers and targets for Rehabilitation

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Duan, Yinan, Wang, Yixuan, Liu, Yonghong, Jin, Zhaohui, Liu, Cui, Yu, Xin, Chen, Keke, Meng, Detao, Xi, Jianing, Fang, Boyan·2022·Molecular Neurobiology
DOI 10.21203/rs.3.rs-2298871/v1

Preprint — published as 10.1007/s12035-023-03268-0 · Paper page

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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 surgical 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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Metadata

Authors
Duan, Y., Wang, Y., Liu, Y., Jin, Z., Liu, C., Yu, X., Chen, K., Meng, D., Xi, J., & Fang, B.
Affiliations
Capital Medical University (CN)
Corresponding author
  • Xi, Jianing
  • Fang, Boyan
ORCID
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2022-12-07
Volume
60
Issue
6
Pages
3261-3276
ISSN
0893-7648 (ISSN-L)
DOI
10.21203/rs.3.rs-2298871/v1
OpenAlex
W4321996948
Cited by
17
References
1
Citations by year
2026: 1 · 2025: 7 · 2024: 5 · 2023: 3
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurobiology (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Capital Medical University (2021-011, 2020-069)
  • Science and Technology Development Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
Parkinson's disease, circular RNA, rehabilitation, blood exosomes, biomarkers, alpha-synuclein aggregation, competing endogenous RNA network, epigenetic regulation, actin cytoskeleton, synaptic structure, inflammation
MeSH terms
RNA, Circular, Humans, Parkinson Disease, RNA, Biomarkers, MicroRNAs, alpha-Synuclein

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