Abrin Toxicity Across the Proteomic Landscape: Mechanisms, Protein Targets, and Therapeutic Challenges

Background: Abrus precatorius is a plant of significant toxicological importance due to the presence of abrin, a highly potent ribosome-inactivating protein. Although the seeds of A. precatorius have been used in traditional medicine in certain regions for anti-inflammatory and antipyretic purposes, abrin is among the most lethal plant-derived toxins known, posing serious public health and biosecurity concerns. Increasing evidence suggests that abrin toxicity extends beyond ribosomal inhibition and involves complex interactions with multiple cellular proteins and pathways. Objectives: This review aims to synthesize and critically evaluate current knowledge of the molecular mechanisms underlying abrin toxicity, with particular focus on its interactions with cellular proteins. It examines lectin-mediated cellular entry, inhibition of protein synthesis, and disruption of key protein classes, including enzymes, receptors, and structural proteins. The review further assesses recent advances in proteomic and multi-omic approaches for identifying abrin-responsive protein targets and dysregulated pathways. Emerging therapeutic strategies, including neutralizing antibodies, immunotoxins, vaccines, and small-molecule inhibitors, are also evaluated, with emphasis on translational challenges and safety considerations. Conclusion: Abrin induces multifactorial toxic effects, including apoptosis, oxidative stress, immune dysregulation, and metabolic dysfunction, thereby contributing to systemic lethality while also highlighting its potential as a targeted anticancer agent. This review provides an integrated overview of abrin’s protein-level interactions and biological effects and underscores the importance of preventive measures, regulatory awareness, and public education to mitigate exposure risks. Overall, the work serves as a comprehensive resource to support future research on targeted therapies, antidote development, and biomedical applications.