Department of Genetics and Cell Physiology, Faculty of Biological Sciences, University of Wroclaw, 50-328, Wroclaw, Poland.
Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, 405 30, Göteborg, Sweden.
Cell Mol Life Sci. 2023 Oct 30;80(11):342. doi: 10.1007/s00018-023-04992-5.
Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.
砷和锑是具有深刻生物学系统和人类健康效应的类金属。这两种元素对细胞和生物体都有毒性，暴露于这些元素会导致多种病理状况，包括癌症和神经退行性疾病。同时，含砷和含锑的化合物被用于治疗多种疾病。尽管这些类金属既能引起疾病，也能治疗疾病，但它们的分子作用模式仍不完全清楚。过去几十年，我们对砷和锑的毒性有了重大的认识进展，强调遗传毒性和蛋白质毒性是发病机制的关键因素。在这篇综述中，我们重点介绍了砷和锑引起毒性的机制，特别关注它们的遗传毒性和蛋白质毒性作用。还描述了细胞在类金属暴露期间维持蛋白质稳定性的机制。此外，我们还探讨了类金属诱导的蛋白质毒性如何促进神经退行性疾病，以及遗传毒性和蛋白质毒性如何相互关联并共同导致蛋白质病。更深入地了解细胞毒性和反应机制及其与发病机制的联系可能会促进疾病预防和治疗策略的发展。
