Background: Mechanisms of neuroprotection encompass energy deficits in brain arising from insufficient oxygen and glucose levels following respiratory failure; ischemia or stroke, which produce metabolic stresses that lead to unconsciousness and seizures; and the effects of general anesthetics. Foremost among those K(+) channels viewed as important for neuroprotection are ATP-sensitive (K(ATP)) channels, which belong to the family of inwardly rectifying K(+) channels (K(ir)) and contain a sulfonylurea subunit (SUR1 or SUR2) combined with either K(ir)6.1 (KCNJ8) or K(ir)6.2 (KCNJ11) channel pore-forming alpha-subunits, and various members of the tandem two-pore or background (K(2P)) K(+) channel family, including K(2P)1.1 (KCNK1 or TWIK1), K(2P)2.1 (KCNK2 or TREK/TREK1), K(2P)3.1 (KCNK3 or TASK), K(2P)4.1 (KCNK4 or TRAAK), and K(2P)10.1 (KCNK10 or TREK2).
Objectives: This review covers patents and patent applications related to inventions of therapeutics, compound screening methods and diagnostics, including K(ATP) channel openers and blockers, as well as K(ATP) and K(2P) nucleic/amino acid sequences and proteins, vectors, transformed cells and transgenic animals. Although the focus of this patent review is on brain and neuroprotection, patents covering inventions of K(ATP) channel openers for cardioprotection, diabetes mellitus and obesity, where relevant, are addressed.
Results/conclusions: Overall, an important emerging therapeutic mechanism underlying neuroprotection is activation/opening of K(ATP) and K(2P) channels. To this end substantial progress has been made in identifying and patenting agents that target K(ATP) channels. However, current K(2P) channels patents encompass compound screening and diagnostics methodologies, reflecting an earlier 'discovery' stage (target identification/validation) than K(ATP) in the drug development pipeline; this reveals a wide-open field for the discovery and development of K(2P)-targeting compounds.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1517/13543770902765151 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The modulation of potassium channels by estrogens facilitates neuroprotection.
Front Cell Dev Biol
October 2022
School of Medicine, Guizhou University, Guiyang, China.
Estrogens, the sex hormones, have the potential to govern multiple cellular functions, such as proliferation, apoptosis, differentiation, and homeostasis, and to exert numerous beneficial influences for the cardiovascular system, nervous system, and bones in genomic and/or non-genomic ways. Converging evidence indicates that estrogens serve a crucial role in counteracting neurodegeneration and ischemic injury; they are thereby being considered as a potent neuroprotectant for preventing neurological diseases such as Alzheimer's disease and stroke. The underlying mechanism of neuroprotective effects conferred by estrogens is thought to be complex and multifactorial, and it remains obscure.
View Article and Find Full Text PDFBeneficial effects of carvedilol modulating potassium channels on the control of glucose.
Biomed Pharmacother
June 2022
Department of Neuroscience, South-Central University for Nationalities, Wuhan 430074, China; School of Medicine, Guizhou University, Guiyang 550025, China. Electronic address:
The increased prevalence of hypertensive patients with type 2 diabetes mellitus (T2DM) is evident worldwide, leading to a higher risk of cardiovascular disease onset, which is substantially associated with disabilities and mortality in the clinic. In order to achieve the satisfyingly clinical outcomes and prognosis, the comprehensive therapies have been conducted with a beneficial effect on both blood pressure and glucose homeostasis, and clinical trials reveal that some kind of antihypertensive drugs such as angiotensin converting enzyme inhibitors (ACE-I) may, at least in part, meet the dual requirement during the disease management. As a nonselective β-blocker, carvedilol is employed for treating many cardiovascular diseases in clinical practice, including hypertension, angina pectoris and heart failure, and also exhibit the effectiveness for glycemic control and insulin resistance.
View Article and Find Full Text PDFPotassium Channels Contributes to Apelin-induced Vasodilation in Rat Thoracic Aorta.
Protein Pept Lett
September 2022
Physiology Department, Bursa Uludag University Medicine School, Bursa, Turkey.
Background: Apelin is a newly discovered peptide hormone and originally discovered endogenous apelin receptor ligand.
Objective: In this study, we aimed to investigate the possible roles of potassium channel subtypes in the vasorelaxant effect mechanisms of apelin.
Methods: The vascular rings obtained from the thoracic aortas of the male Wistar Albino rats were placed into the isolated tissue bath system.
Physiological role of K channels in irisin-induced vasodilation in rat thoracic aorta.
Peptides
January 2022
Department of Physiology, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey. Electronic address:
Irisin, an exercise-induced myokine, has been shown to have a peripheral vasodilator effect. However, little is known about the mechanisms underlying its effects. In this study, it was aimed to investigate the vasoactive effects of irisin on rat thoracic aorta, and the hypothesis that voltage-gated potassium (K) channels, ATP-sensitive potassium (K) channels, small-conductance calcium-activated potassium (SK) channels, large-conductance calcium-activated potassium (BK) channels, intermediate-conductance calcium-activated potassium (IK) channels, inward rectifier potassium (K) channels, and two-pore domain potassium (K) channels may have roles in these effects.
View Article and Find Full Text PDFPotassium channels on smooth muscle as a molecular target for plant-derived Resveratrol.
Cell Mol Biol (Noisy-le-grand)
June 2020
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, 11129 Belgrade, Serbia.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a phytoalexin present in a variety of plant species. Resveratrol has a wide spectrum of pharmacologic properties, and it exhibits versatile biological effects on different human and animal models. The studies have shown that potassium (K) channels can be potential targets in the mechanism of resveratrol action.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!