Amir Gharib , Carlee Marquez , Maria Meseguer-Beltran , Sandra Sanchez-Sarasua , Ana M Sanchez-Perez
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引用次数: 0
摘要
脱落酸(ABA)是一种植物激素,传统上因其在植物应激反应中的作用而为人们所熟知,近来它在哺乳动物防御机制中也扮演着重要角色。与植物一样,哺乳动物的各种细胞类型也会合成脱落酸以应对特定的健康挑战,但其确切的途径仍未完全阐明。ABA 与炎症和胰岛素信号的调节有关,促使人们对其作为各种疾病治疗剂的潜力进行广泛研究。ABA 通过其受体,特别是 PPAR-γ 和 LANCL-2 发挥作用,这些受体是调节众多途径的信号枢纽。通过这些相互作用,ABA 对哺乳动物的健康产生了深远的影响,而新的 ABA 靶点也在不断被发现。在本手稿中,我们回顾了有关 ABA 在细胞培养物中的合成和释放、受 ABA 调节的信号通路以及这些通路如何在临床前模型中影响健康等方面的研究。此外,我们还重点介绍了最近的一些研究,这些研究表明,测量人体液中的 ABA 水平可作为病理条件下的一种有用生物标志物,为了解疾病进展和治疗效果提供洞察力。这篇综合性综述概述了目前对 ABA 在哺乳动物病理生理学中作用的认识,指出了知识空白,特别是有关 ABA 在哺乳动物体内的生物合成和代谢的知识。此外,本研究还强调了临床试验的必要性,以验证基于 ABA 的疗法的有效性及其作为各种疾病生物标志物的可靠性。
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.
期刊介绍:
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.