Activation of the sympatho-β-adrenergic receptor (βAR) system is the hallmark of heart disease with adverse consequences that facilitate the onset and progression of heart failure (HF). Use of β-blocking drugs has become the front-line therapy for HF. Last decade has witnessed progress in research demonstrating a pivotal role of Hippo pathway in cardiomyopathy and HF. Clinical studies have revealed myocardial Hippo pathway activation/YAP-TEAD1 inactivation in several types of human cardiomyopathy. Experimental activation of cardiac Hippo signaling or inhibition of YAP-TEAD1 have been shown to leads dilated cardiomyopathy with severe mitochondrial dysfunction and metabolic reprogramming. Studies have also convincingly shown that stimulation of βAR activates cardiac Hippo pathway with inactivation of the down-stream effector molecules YAP/TAZ. There is strong evidence for the adverse consequences of the βAR-Hippo signaling leading to HF. In addition to promoting cardiomyocyte death and fibrosis, recent progress is the demonstration of mitochondrial dysfunction and metabolic reprogramming mediated by βAR-Hippo pathway signaling. Activation of cardiac βAR-Hippo signaling is potent in downregulating a range of mitochondrial and metabolic genes, whereas expression of pro-inflammatory and pro-fibrotic factors are upregulated. Coupling of βAR-Hippo pathway signaling is mediated by several kinases, mechanotransduction and/or Ca²⁺ signaling, and can be blocked by β-antagonists. Demonstration of the converge of βAR signaling and Hippo pathway bears implications for a better understanding on the role of enhanced sympathetic nervous activity, efficacy of β-antagonists, and metabolic therapy targeting this pathway in HF. In this review we summarize the progress and discuss future research directions in this field.

2024-06-01·Heliyon

Research progress of nano delivery systems for intraocular pressure lowering drugs

Review

作者: Zhao, Yang ; Zhang, Xinyue ; Wu, Ping ; Duan, Xuanchu ; Zhou, Xiaoyu ; Liao, Li ; Zhou, Dengming ; Chen, Baihua

Glaucoma is a chronic ocular disease characterized by optic atrophy and visual field defect. The main risk factor for glaucoma onset and progression is elevated intraocular pressure, which is caused by increased aqueous humor outflow resistance. Currently, the primary method for glaucoma therapy is the use of intraocular pressure lowering drugs. However, these drugs, when administered through eye drops, have low bioavailability, require frequent administration, and often result in adverse effects. To overcome these challenges, the application of nanotechnology for drug delivery has emerged as a promising approach. Nanoparticles can physically adsorb, encapsulate, or chemically graft drugs, thereby improving their efficacy, retention time, and reducing adverse reactions. Moreover, nanotechnology has opened up new avenues for ocular administration. This article provides a comprehensive review of nano systems for intraocular pressure lowering drugs, encompassing cholinergic agonists, β-adrenergic antagonists, α-adrenergic agonists, prostaglandin analogs, carbonic anhydrase inhibitors, Rho kinase inhibitors, and complex preparations. The aim is to offer novel insights for the development of nanotechnology in the field of intraocular pressure lowering drugs.

2020-10-01·Seminars in Pediatric Neurology4区 · 医学

The Role of the Noradrenergic System in Autism Spectrum Disorders, Implications for Treatment

4区 · 医学

Review

作者: Beversdorf, David Q

Autism spectrum disorder (ASD) is frequently associated with anxiety and hyperarousal. While the pathological changes in the noradrenergic system in ASD are not entirely clear, a number of functional indices of the sympathetic/parasympathetic balance are altered in individuals with ASD, often with a high degree of inter-individual variability. The neuropsychopharmacological effects of α₂ agonists and β-adrenergic antagonists make agents targeting these receptors of particular interest. α₂ agonists have shown beneficial effects for attention deficit hyperactivity disorder (ADHD) and in other domains in individuals with ASD, but effects on core ASD symptoms are less clear. Case series and single dose psychopharmacological challenges suggest that treatment with β-adrenergic antagonists has beneficial effects on language and social domains. Additionally, psychophysiological markers and premorbid anxiety may predict response to these medications. As a result, β-adrenergic antagonists are currently being utilized in a clinical trial for improving core symptoms as well as anxiety in individuals with ASD.

100 项与 ROR-β antagonists (Orphagen) 相关的药物交易

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