Abscisic acid, an evolutionary conserved hormone: Biosynthesis, therapeutic and diagnostic applications in mammals

Abscisic acid (ABA), a phytohormone traditionally recognized for its role in plant stress responses, has recently emerged as a significant player in mammalian defense mechanisms. Like plants, various mammalian cell types synthesize ABA in response to specific health challenges, although the precise pathways remain not fully elucidated. ABA is associated with the regulation of inflammation and insulin signaling, prompting extensive research into its potential as a therapeutic agent for various diseases. ABA exerts its effects through its receptors, particularly PPAR-γ and LANCL-2, which serve as signaling hubs regulating numerous pathways. Through these interactions, ABA profoundly impacts mammalian health, and new ABA targets continue to be identified. Numerous studies in animal models demonstrate ABA's benefit in managing conditions such as neurological and psychiatric disorders, cancer, and malaria infections, all of which involve significant inflammatory dysregulation. In this manuscript we review the studies covering ABA synthesis and release in cell cultures, the signaling pathways regulated by ABA, and how these impact health in preclinical models. Furthermore, we highlight recent research suggesting that measuring ABA levels in human body fluids could serve as a useful biomarker for pathological conditions, providing insights into disease progression and treatment efficacy. This comprehensive review outlines the current understanding of ABA in mammalian pathophysiology, identifying gaps in knowledge, particularly concerning ABA biosynthesis and metabolism in mammals. In addition, this study emphasizes the need for clinical trials to validate the effectiveness of ABA-based therapies and its reliability as a biomarker for various diseases.