Center for Genetic Medicine Research, Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Department of Genomics and Precision Medicine, The George Washington University of Medicine and Health Sciences, Washington, DC, USA.
Nat Commun. 2024 Sep 6;15(1):7811. doi: 10.1038/s41467-024-52136-5.
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.
科松病是一种被忽视的神经麻痹性疾病，与食用（木薯）中毒有关，影响着撒哈拉以南非洲地区最贫穷的儿童和育龄妇女。尽管人们已经了解了导致科松病的饮食因素，但引发这种疾病的分子标记物和机制仍不清楚。为了确定与疾病状态相关的潜在蛋白质生物标志物，我们从两个独立的刚果人群中采集了血浆，一个是发现队列（n=60），另一个是验证队列（n=204），这两个队列分别在 10 年前和 10 年后进行了多次高通量检测。我们发现，谷胱甘肽过氧化物酶 3（GPx3），一种重要的基于血浆的抗氧化酶，是唯一在两个队列中受影响和未受影响参与者之间存在显著差异且含量丰富的蛋白质，在患有科松病的患者中观察到其含量大量减少。我们的研究结果表明，关键抗氧化机制的减少可能是科松病发展的生物学风险因素，特别是那些涉及谷胱甘肽过氧化物酶家族的途径。
