Safreena Narukkottil, Chandra Goutam, Thirumalaikumar Venkatesh P, Cannon Jason
Purdue University, West Lafayette, IN 47907, USA; Inter University Centre for Biomedical Research & Super Speciality Hospital, Mahatma Gandhi University campus at Thalappady, Rubber Board PO, Kottayam, Kerala 686009, India.
Inter University Centre for Biomedical Research & Super Speciality Hospital, Mahatma Gandhi University campus at Thalappady, Rubber Board PO, Kottayam, Kerala 686009, India.
Toxicology. 2025 Aug 8;518:154260. doi: 10.1016/j.tox.2025.154260.
Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic compounds known for their high chemical stability, resistance to degradation. This class includes thousands of different compounds widely used in various products like non-stick cookware, water-repellent fabrics, food packaging, firefighting foam, and many personal care products. While these properties contribute to their industrial utility, they also pose significant environmental and health concerns due in part to long environmental and biological half-lives. PFAS contamination has been widely reported in water sources and soil, along with reports of bioaccumulation in the blood and tissues of living organisms. These chemicals have been linked to a range of health effects, including potential risks to cancer, neurotoxicity, and developmental disorders. Given their broad involvement in disease pathology, it is critical to investigate the underlying molecular mechanisms of PFAS toxicity. This review evaluates current research on the impact of various PFAS on different proteins, their post-translational modifications (PTMs), and the effects on cellular signalling pathways. It also reviews proteomic studies conducted over the years that aim to elucidate these protein-level changes, while highlighting existing gaps in the field. Despite growing attention to PFAS toxicity, significant advances are required in elucidating the primary mechanisms of toxic action. Studying PFAS effects from a proteome perspective could be very promising. In particular, the lack of organ-specific proteomic data, including studies on distinct brain regions and PTM-specific profiling, represents a critical area for future research.
全氟和多氟烷基物质（PFAS）是一类以高化学稳定性和抗降解性著称的合成化合物。这类物质包括数千种不同的化合物，广泛应用于各种产品中，如不粘锅炊具、防水织物、食品包装、消防泡沫以及许多个人护理产品。虽然这些特性有助于它们在工业上的应用，但它们也引发了重大的环境和健康问题，部分原因是其在环境和生物中的半衰期较长。PFAS污染在水源和土壤中已被广泛报道，同时也有关于其在生物体血液和组织中生物累积的报道。这些化学物质与一系列健康影响有关，包括癌症、神经毒性和发育障碍等潜在风险。鉴于它们广泛涉及疾病病理学，研究PFAS毒性的潜在分子机制至关重要。本综述评估了当前关于各种PFAS对不同蛋白质的影响、其翻译后修饰（PTM）以及对细胞信号通路影响的研究。它还回顾了多年来旨在阐明这些蛋白质水平变化的蛋白质组学研究，同时突出了该领域现有的差距。尽管对PFAS毒性的关注日益增加，但在阐明其主要毒性作用机制方面仍需要取得重大进展。从蛋白质组学角度研究PFAS的影响可能非常有前景。特别是，缺乏器官特异性蛋白质组学数据，包括对不同脑区的研究和PTM特异性分析，是未来研究的一个关键领域。
