RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease

Athira Anirudhan,Ashutosh Sharma,Ram Murugesan,S Manjunath Kamath,Prabu Paramasivam,Kalaivani Manokaran,Shiek S S J Ahmed,Paola Isabel Angulo-Bejarano

doi:10.3389/fnins.2021.631892

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease with no definite molecular markers for diagnosis. Metal exposure may alter cellular proteins that contribute to PD. Exploring the cross-talk between metal and its binding proteins in PD could reveal a new strategy for PD diagnosis. We performed a meta-analysis from different PD tissue microarray datasets to identify differentially expressed genes (DEGs) common to the blood and brain. Among common DEGs, we extracted 280 metalloprotein-encoding genes to construct protein networks describing the regulation of metalloproteins in the PD blood and brain. From the metalloprotein network, we identified three important functional hubs. Further analysis shows 60S ribosomal protein L6 (RPL6), a novel intermediary molecule connecting the three hubs of the metalloproteins network. Quantitative real-time PCR analysis showed that RPL6 was downregulated in PD peripheral blood mononuclear cell (PBMC) samples. Simultaneously, trace element analysis revealed altered serum zinc and magnesium concentrations in PD samples. The Pearson’s correlation analysis shows that serum zinc and magnesium regulate the RPL6 gene expression in PBMC. Thus, metal-regulating RPL6 acts as an intermediary molecule connecting the three hubs that are functionally associated with PD. Overall our study explores the understanding of metal-mediated pathogenesis in PD, which provides a serum metal environment regulating the cellular gene expression that may light toward metal and gene expression-based biomarkers for PD diagnosis.

Highlights

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases occurring at the substantia nigra (SNc) region of the central nervous system (Lang and Lozano, 1998)
We used keywords related to PD to search for the gene expression studies conducted in the brain and blood in the databases
To identify common differentially expressed genes (DEGs) in the blood and brain between PD and control samples, the datasets from the blood and brain were meta-analyzed with the p < 0.05 as cutoff in Fisher’s exact test

Summary

Introduction

Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases occurring at the substantia nigra (SNc) region of the central nervous system (Lang and Lozano, 1998). Degeneration of neurons causes resting bradykinesia, postural instability, rigidity, and tremor. These symptoms, along with the Movement Disorder Society (MDS)-Unified Parkinson’s Disease Rating Scale (UPDRS), help in the clinical diagnosis of Regulators of Metalloprotein in Parkinson’s Disease. Imaging techniques such as CT, PET, and MRI showed benefit in PD detection (Pagano et al, 2016). Advances in research establish the underlying PD pathogenesis that allows determining molecular markers for diagnosis. Many studies implement high-throughput technologies, which generate vast biological data in genomics, transcriptomics, proteomics, and metabolomics. These biological resources publically available in repositories are useful for further investigation. Integrating these available resources may provide several previously unknown mechanisms of PD, which enables biomarker discovery

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