Capital Medical University School of Beijing Rehabilitation Medicine, Capital Medical University, Beijing, China.
Parkinson Medical Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
Mol Neurobiol. 2023 Jun;60(6):3261-3276. doi: 10.1007/s12035-023-03268-0. Epub 2023 Feb 25.
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.
在临床实践中，帕金森病（PD）的潜在发病机制尚不清楚。环状 RNA（circRNA）具有良好的生物学特性，可作为生物标志物。康复作为药物和手术之外的第三种治疗方法已被证明具有临床疗效，但遗传水平上的康复效率生物标志物仍缺乏。在这项研究中，我们鉴定了 PD 患者和健康对照（HC）外周血外泌体中差异表达的 circRNA，并确定了这些 circRNA 在康复后是否发生变化，以探索受影响的竞争性 RNA 网络和表观遗传机制。我们发现，与 HCs 相比，PD 患者中有 558 个上调和 609 个下调的 circRNA，与康复前相比，PD 患者中有 3398 个上调和 479 个下调的 circRNA，与 HCs 相比，PD 患者中有 3721 个上调和 635 个下调的 circRNA。基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，差异表达的 circRNA 可能通过影响 α-突触核蛋白（a-syn）的聚集来影响细胞肌动蛋白骨架和突触结构的稳定性。我们选择了在 PD 患者中过度表达的两个 circRNA 进行验证（hsa_circ_0001535 和 hsa_circ_0000437）；结果表明，它们的表达水平在康复后均不同程度降低（p < 0.05）。经过网络分析，我们认为 hsa_circ_0001535 可能与 a-syn 的聚集有关，而 hsa_circ_0000437 可能通过海绵效应作用于 hsa-let-7b-5p 或 hsa-let-7c-5p 引起炎症反应。我们的研究结果表明，康复可以通过表观遗传手段减轻 PD 的病理过程。
