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

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....

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Autores principales: Anirudhan, Athira, Angulo-Bejarano, Paola Isabel, Paramasivam, Prabu, Manokaran, Kalaivani, Kamath, S. Manjunath, Murugesan, Ram, Sharma, Ashutosh, Ahmed, Shiek S. S. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006920/
https://www.ncbi.nlm.nih.gov/pubmed/33790735
http://dx.doi.org/10.3389/fnins.2021.631892
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author Anirudhan, Athira
Angulo-Bejarano, Paola Isabel
Paramasivam, Prabu
Manokaran, Kalaivani
Kamath, S. Manjunath
Murugesan, Ram
Sharma, Ashutosh
Ahmed, Shiek S. S. J.
author_facet Anirudhan, Athira
Angulo-Bejarano, Paola Isabel
Paramasivam, Prabu
Manokaran, Kalaivani
Kamath, S. Manjunath
Murugesan, Ram
Sharma, Ashutosh
Ahmed, Shiek S. S. J.
author_sort Anirudhan, Athira
collection PubMed
description 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.
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spelling pubmed-80069202021-03-30 RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease Anirudhan, Athira Angulo-Bejarano, Paola Isabel Paramasivam, Prabu Manokaran, Kalaivani Kamath, S. Manjunath Murugesan, Ram Sharma, Ashutosh Ahmed, Shiek S. S. J. Front Neurosci Neuroscience 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. Frontiers Media S.A. 2021-03-11 /pmc/articles/PMC8006920/ /pubmed/33790735 http://dx.doi.org/10.3389/fnins.2021.631892 Text en Copyright © 2021 Anirudhan, Angulo-Bejarano, Paramasivam, Manokaran, Kamath, Murugesan, Sharma and Ahmed. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Anirudhan, Athira
Angulo-Bejarano, Paola Isabel
Paramasivam, Prabu
Manokaran, Kalaivani
Kamath, S. Manjunath
Murugesan, Ram
Sharma, Ashutosh
Ahmed, Shiek S. S. J.
RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease
title RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease
title_full RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease
title_fullStr RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease
title_full_unstemmed RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease
title_short RPL6: A Key Molecule Regulating Zinc- and Magnesium-Bound Metalloproteins of Parkinson’s Disease
title_sort rpl6: a key molecule regulating zinc- and magnesium-bound metalloproteins of parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006920/
https://www.ncbi.nlm.nih.gov/pubmed/33790735
http://dx.doi.org/10.3389/fnins.2021.631892
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