Parkinson’s disease (PD) affects 1% of people over 60, and long-term levodopa treatment can cause side effects. Early diagnosis is of great significance in slowing down the pathological process of PD. Multiple pieces of evidence showed that non-coding RNAs (ncRNAs) could participate in the progression of PD pathology. Pyroptosis is known to be regulated by ncRNAs as a key pathological feature of PD. Therefore, evaluating ncRNAs and pyroptosis-related proteins in serum could be worthy biomarkers for early diagnosis of PD. NcRNAs and pyroptosis/inflammation mRNA levels were measured with reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Luciferase assays were performed to confirm GSDME as a target of miR-675-5p and HMGB1 as a target of miR-1247-5p. In the serum of healthy controls (n = 106) and PD patients (n = 104), RT-qPCR was utilized to assess miR-675-5p, miR-1247-5p, and two related ncRNAs (circSLC8A1and lncH19) levels. The enzyme-linked immunosorbent assay measured serum levels of pyroptosis-related proteins in controls (n = 54) and PD patients (n = 70). Our data demonstrated that miR-675-5p and miR-1247-5p significantly changed in PD neuron and animal models. Overexpressed miR-675-5p or downregulated miR-1247-5p could regulate pyroptosis and inflammation in PD neuron models. Using the random forest algorithm, we constructed a classifier based on PD neuron-pyroptosis pathology (four ncRNAs and six proteins) having better predictive power than single biomarkers (AUC = 92%). Additionally, we verified the performance of the classifier in early-stage PD patients (AUC ≥ 88%). Serum pyroptosis-related ncRNAs and proteins could serve as reliable, inexpensive, and non-invasive diagnostic biomarkers for PD. All participants were from the same region. Additionally, longitudinal studies in the aged population are required to explore the practical application value of the classifier.

中文翻译：

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焦亡介导的生物标志物模式：帕金森病的新兴诊断方法

帕金森病 (PD) 影响 1% 的 60 岁以上人群，长期左旋多巴治疗会引起副作用。早期诊断对于减缓PD的病理进程具有重要意义。多项证据表明非编码 RNA (ncRNA) 可能参与 PD 病理的进展。众所周知，焦亡是 PD 的一个关键病理特征，受到 ncRNA 的调节。因此，评估血清中的 ncRNA 和焦亡相关蛋白可能成为 PD 早期诊断的有价值的生物标志物。使用逆转录酶定量聚合酶链反应 (RT-qPCR) 测量 NcRNA 和细胞焦亡/炎症 mRNA 水平。进行荧光素酶测定以确认 GSDME 作为 miR-675-5p 的靶标和 HMGB1 作为 miR-1247-5p 的靶标。在健康对照 (n = 106) 和 PD 患者 (n = 104) 的血清中，利用 RT-qPCR 评估 miR-675-5p、miR-1247-5p 和两种相关 ncRNA（circSLC8A1 和 lncH19）水平。酶联免疫吸附试验测量了对照组 (n = 54) 和 PD 患者 (n = 70) 的血清焦亡相关蛋白水平。我们的数据表明，miR-675-5p 和 miR-1247-5p 在 PD 神经元和动物模型中发生显着变化。过表达的 miR-675-5p 或下调的 miR-1247-5p 可以调节 PD 神经元模型中的细胞焦亡和炎症。使用随机森林算法，我们构建了一个基于 PD 神经元焦亡病理学（四种 ncRNA 和六种蛋白质）的分类器，其预测能力比单一生物标志物更好（AUC = 92%）。此外，我们还验证了分类器在早期 PD 患者中的性能 (AUC ≥ 88%)。血清焦亡相关的 ncRNA 和蛋白质可以作为可靠、廉价且非侵入性的 PD 诊断生物标志物。所有参与者都来自同一地区。此外，还需要对老年人群进行纵向研究，以探索分类器的实际应用价值。