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Coordinated modification in expression levels of HSPA1A/B, DGKH, and NOTCH2 in Parkinson’s patients’ blood and substantia nigra as a diagnostic sign: the transcriptomes’ relationship

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Abstract

Background

Diagnosis of Parkinson’s disease (PD) is associated with a vast number of challenges. This study aimed to assess the overlap of PD patients’ transcriptomes in the substantia nigra (SN) with peripheral blood mononuclear cells (PBMCs) to discover potential biomarkers for diagnosis.

Methods

GEO data were used to select genes with significant changes in expression level in the SN region and eligible studies. Also, transcriptome data related to blood of PD patients with other neurodegenerative diseases (ND) was considered. Differential expression genes between PD and control were evaluated in the SN and blood, and RT-qPCR was applied to validate the findings.

Results

At the expression level, no significant similarity in long non-coding RNA was found between the patients’ SN and blood. While in silico results revealed 16 common mRNAs in SN and blood with significant expression levels. Among all overexpressed mRNAs, HSPA1A/B expression level had the highest expression difference between control and PD samples. Moreover, DGKH had the highest score of down-regulated genes in both blood and SN. The NOTCH pathway had the highest score pathway among up-regulated pathways, and the expression levels of NOTCH2, H4C8, and H2BC21 associated with this pathway had the most ability to separate the control and PD populations. Furthermore, RT-qPCR results revealed that HSPA1A/B, NOTCH2, and H4C8 were overexpressed in PD PBMCs, while DGKH expression levels were lower compared to controls.

Conclusion

Our findings indicate that expression levels of HSPA1A/B, DGKH, and NOTCH2 could be applied as candidate biomarkers to diagnose PD patients in the SN region and PBMCs.

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Data availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

PD:

Parkinson’s disease

SN:

Substantia nigra

PBMCs:

Peripheral blood mononuclear cells

ND:

Neurodegenerative diseases

HD:

Huntington’s disease

MSA:

Multiple system atrophy

PSP:

Progressive supranuclear palsy

ROC:

Receiver operating characteristic

GSEA:

Gene set enrichment analysis

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Acknowledgements

We thank Mr. Mohammad Mahdevar for his association in RNA-seq and microarray analysis. Also, we thank our colleagues for their helpful discussions in this study. This research was partly supported by TIG Grant Committee (Avicenna Center of excellence) and Isfahan Research Network (project title: Neurodegenerative Diseases Research Group) to K.G.

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran

    Leila Asad Samani

  2. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Azadi Sq., Hezar Jerib Ave, P.O. Code, Isfahan, 81746-73441, Iran

    Kamran Ghaedi

  3. Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran

    Ahmad Majd

  4. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Maryam Peymani

  5. Department of Neurology and Isfahan Neurosurgery Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Masoud Etemadifar

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  1. Leila Asad Samani
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Contributions

The design, sample collection, and conceptualization of study and methodology were done by Leila Asad Samani and Maryam Peymani. Data mining, formal analysis, and investigation were performed by Leila Asad Samani. Supervision, validation, and visualization were done by Maryam Peymani and Kamran Ghaedi. Interpretation of the obtained information was done by Maryam Peymani and sample collection by Masoud Etemadifar. The manuscript was written by Leila Asad Samani. Review, editing, and approval were by Maryam Peymani, Kamran Ghaedi, and Ahmad Majd. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Kamran Ghaedi or Ahmad Majd.

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Ethics approval

All protocols for the usage of human samples in this study were reviewed and approved by the Biomedical Ethics Committee of the Islamic Azad University—North Tehran Branch and also complies with the Ethics Code of IR.IAU.TNB.REC.1400.007 in accordance with the relevant guidelines and regulations for using of human samples.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Competing interests

The authors declare no competing interests.

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Asad Samani, L., Ghaedi, K., Majd, A. et al. Coordinated modification in expression levels of HSPA1A/B, DGKH, and NOTCH2 in Parkinson’s patients’ blood and substantia nigra as a diagnostic sign: the transcriptomes’ relationship. Neurol Sci 44, 2753–2761 (2023). https://doi.org/10.1007/s10072-023-06738-4

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  • DOI: https://doi.org/10.1007/s10072-023-06738-4

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