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

doi:10.1186/s11658-023-00516-y

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

Cell Mol Biol Lett. 2024 Jan 3;29(1):7. doi: 10.1186/s11658-023-00516-y.

Authors

Junhan Liang¹, Zhirong Wan², Cheng Qian¹, Madiha Rasheed¹, Changling Cao¹, Jingyan Sun³, Xuezhe Wang¹, Zixuan Chen⁴, Yulin Deng⁵

Affiliations

¹ Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Medical Technology, Beijing Institute of Technology, Zhongguancun South Street, Haidian District, Beijing, 100081, People's Republic of China.
² Department of Neurology, Aerospace Center Hospital, Beijing, 100049, People's Republic of China.
³ School of Life Sciences, Beijing Institute of Technology, Beijing, 100081, People's Republic of China.
⁴ Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Medical Technology, Beijing Institute of Technology, Zhongguancun South Street, Haidian District, Beijing, 100081, People's Republic of China. zx-chen@bit.edu.cn.
⁵ Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, School of Medical Technology, Beijing Institute of Technology, Zhongguancun South Street, Haidian District, Beijing, 100081, People's Republic of China. deng@bit.deu.cn.

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.

Keywords: Biomarker patterns; Machine learning; Parkinson’s disease.

MeSH terms

Aged
Animals
Biomarkers
Humans
Inflammation
MicroRNAs* / metabolism
Parkinson Disease* / diagnosis
Parkinson Disease* / genetics
Pyroptosis

Substances

MicroRNAs
Biomarkers
MIRN1247 microRNA, human
MIRN675 microRNA, human

Abstract

MeSH terms

Substances

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