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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. Copyright © 2021 Anirudhan, Angulo-Bejarano, Paramasivam, Manokaran, Kamath, Murugesan, Sharma and Ahmed.


Athira Anirudhan, Paola Isabel Angulo-Bejarano, Prabu Paramasivam, Kalaivani Manokaran, S Manjunath Kamath, Ram Murugesan, Ashutosh Sharma, Shiek S S J Ahmed. RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson's Disease. Frontiers in neuroscience. 2021;15:631892

PMID: 33790735

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