Scientists establish a new ion channel drug screening method September 29, 2018 Source: Shanghai Institute of Life Sciences, Chinese Academy of Sciences On September 26, the journal Nature-Communication published the Institute of Neuroscience of the Chinese Academy of Sciences, the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences, the State Key Laboratory of Neuroscience, Cai Shiqing Research Group, and Beijing Anzhen Hospital, Capital Medical University. Professor Lan Feng teamed up with the research paper entitled "Using Ion Channel Disease Nematode Model to Screen Small Molecular Compounds That Control Ion Channel Function". This study constructed a high-throughput screening method for targeting ion channel compounds in small animal systems, identified compounds that restore the function of pathogenic ion channel mutants, and elucidated its mechanism of action, providing treatment for ion channel diseases. A new strategy. Ion channels provide a pathway for specific ions to enter and exit cells, which are an important part of the molecular basis of the electrical activity of an organism. Ion channels are involved in the regulation of electrical signaling in the nervous system and play a key role in important physiological processes such as heartbeat. Up to 60 ion channels are known to be associated with human diseases or dysfunctions such as epilepsy and arrhythmias. Hereditary gene mutations cause ion channel dysfunction mainly through four mechanisms: 1. Altering the transcription and translation of genes; 2. Involving ion channel protein folding assembly abnormalities, membrane transport defects; 3. Changing ion channel gating and power Learning characteristics; 4, changing the ion selectivity of the ion channel. Therefore, restoring the function of different ion channel pathogenic mutants requires different strategies to achieve precise treatment of ion channel diseases. Currently, ion channel compound screening methods focus on compounds that modulate ion channel gating and kinetics (such as blockers and activators), while studies on regulatory ion channel biosynthesis (Biogenesis) compounds are rare. However, more and more studies have shown that genetic mutations lead to abnormal ion channel folding, which in turn causes protein retention in the endoplasmic reticulum, which is an important pathogenic mechanism of ion channel disease. Therefore, there is an urgent need to establish a method for high-throughput screening of compounds that modulate ion channel function under physiological conditions from different levels (electrophysiological properties and biological processes, etc.). The hERG potassium channel mainly mediates the repolarization process of action potentials of cardiomyocytes, and its abnormal function can lead to long QT syndrome (a kind of arrhythmia disease) and even cause sudden death. The UNC-103 potassium channel of the model animal nematode (C. elegans) is highly homologous to human ERG, and controls important behaviors such as nematode movement and spawning. In this study, the researchers expressed human hERG potassium channels in nematodes, and enhanced potassium channel function significantly altered the excitability of nematode neurons and muscle cells, causing nematodes to produce significant behavioral defects (such as spawning and exercise). The change of hERG potassium channel function will lead to changes in nematode behavior, which facilitates the screening of ion channel compounds. By observing the behavior of nematodes and combining the corresponding fluorescent protein markers, the researchers screened about 14,800 small molecule compounds, and successfully found the compound ALA that inhibits hERG channel membrane transport and the compounds Prostratin and IDB that restored the transport-deficient hERGA561V channel function. Prostratin and IDB promote hHGA561V channel mutant membrane trafficking, enhance channel function, and correct electrophysiological abnormalities in a cardiomyocyte model in which human induced pluripotent stem cells (hiPSC) differentiate into long QT syndrome. Further studies showed that Prostratin and IDB improved hERGA561V function by activating PKCé€è—•13峄峄峄S606 locus in the ERG channel. The screening method of the nematode ion channel compound established in this study has the advantages of simple construction, simple operation, high throughput and low cost. Combined with the high-throughput analysis platform for nematode behavior that has been developed by the research team, this method based on the nematode ion channel disease model is expected to play an important role in ion channel drug development. The research work was mainly completed by Ph.D. students Jiang Qiang and Li Kai under the guidance of Cai Shiqing and Lan Feng. Lu Wenjing of Beijing Anzhen Hospital and Li Shuang of the Ding Qiurong Research Group of Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences participated in the study. The work was supported by the Strategic Science and Technology Special Project of the Chinese Academy of Sciences, the National Natural Science Foundation and the Fund Committee. Legend: A, A general schematic diagram of a strategy for screening for channel compounds in a nematode channel disease model. B. Schematic diagram of a strategy for screening for channel blockers and activators or functional correctors (functions capable of restoring mutant ion channels) using transgenic nematodes.
Nasal laser is SMALL, LIGHTWEIGHT AND CONVENIENT - Small yet powerful nasal treatment device. It is so small that you can take it everywhere in your pocket or purse making sure you are protected from allergy ANYWHERE ANYTIME!
Nasal laser was developed by a team of scientists and doctors specializing in phototherapy and photobiology. it uses the healing powers of Low-Level laser light 650nm red light. It is clinically proven and its efficacy is supported by clinical and scientific data.
it effectively relieves pet allergies, hay fever and allergic rhinitis without drugs or side effects.
Rhinitis Laser Therapy Device, Rhinitis Laser Apparatus,Rhinitis Allergy,Nasal Laser Light Therapy,Nasal Laser Therapy Device,Nasal Laser Treatment Shenzhen Guangyang Zhongkang Technology Co., Ltd. , https://www.szlighttherapymachine.com
Scientists establish a new ion channel drug screening method