The pyroptosis mediated biomarker pattern: an emerging diagnostic approach for Parkinson’s disease

Junhan Liang, Zhirong Wan, Cheng Qian, Madiha Rasheed, Changling Cao, Jingyan Sun, Xuezhe Wang, Zixuan Chen*, Yulin Deng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: 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. Methods: 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). Results: 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%). Conclusion: Serum pyroptosis-related ncRNAs and proteins could serve as reliable, inexpensive, and non-invasive diagnostic biomarkers for PD. Limitations: 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.

Original languageEnglish
Article number7
JournalCellular and Molecular Biology Letters
Volume29
Issue number1
DOIs
Publication statusPublished - Dec 2024

Keywords

  • Biomarker patterns
  • Machine learning
  • Parkinson’s disease

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