Glutathione peroxidase 3 is a potential biomarker for konzo

Matthew S. Bramble (), Victor Fourcassié, Neerja Vashist, Florence Roux-Dalvai, Yun Zhou, Guy Bumoko, Michel Lupamba Kasendue, D’Andre Spencer, Hilaire Musasa Hanshi-Hatuhu, Vincent Kambale-Mastaki, Rafael Vincent M. Manalo, Aliyah Mohammed, David R. McIlwain, Gary Cunningham, Marshall Summar, Michael J. Boivin, Ljubica Caldovic, Eric Vilain, Dieudonne Mumba-Ngoyi, Desire Tshala-Katumbay () and Arnaud Droit ()
Additional contact information
Matthew S. Bramble: Children’s National Hospital
Victor Fourcassié: CHU de Québec - Université Laval Research Center
Neerja Vashist: UCLA
Florence Roux-Dalvai: CHU de Québec - Université Laval Research Center
Yun Zhou: Children’s National Hospital
Guy Bumoko: Kinshasa University
Michel Lupamba Kasendue: Institut National de Recherche Biomédicale (INRB)
D’Andre Spencer: Children’s National Hospital
Hilaire Musasa Hanshi-Hatuhu: Kinshasa University
Vincent Kambale-Mastaki: Institut National de Recherche Biomédicale (INRB)
Rafael Vincent M. Manalo: University of the Philippines, Manila, Ermita
Aliyah Mohammed: Children’s National Hospital
David R. McIlwain: University of Nevada, Reno School of Medicine
Gary Cunningham: Children’s National Hospital
Marshall Summar: Children’s National Hospital
Michael J. Boivin: Michigan State University
Ljubica Caldovic: Children’s National Hospital
Eric Vilain: University of California
Dieudonne Mumba-Ngoyi: Institut National de Recherche Biomédicale (INRB)
Desire Tshala-Katumbay: Institut National de Recherche Biomédicale (INRB)
Arnaud Droit: CHU de Québec - Université Laval Research Center

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the world’s poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.

Date: 2024
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DOI: 10.1038/s41467-024-52136-5

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