Cell: Scientists develop systems that target phosphatase
August 1, 2018 Source: Biological Exploration of: exploration bacteria
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Phosphatase includes both acidic and basic. Doctors can test specific diseases such as cancer by testing these two enzymes in the body. In previous pharmacological studies, phosphatase was never considered to be undruggable, but a recent Cell study said that scientists have developed a system that targets phosphatase and succeeded in mouse experiments. verification. This discovery gives them the opportunity to screen for drugs that target specific phosphatases.
Related research was published in the journal Cell on July 26th, and Dr. Anne Bertolotti of the Molecular Biology Medical Research Council (MRC) in the United Kingdom was the author of the paper.
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Phosphatase is a key part of cellular signaling (on or off). Most signals start with an activation signal—usually starting with a kinase that attaches a chemical label (phosphate group) to a particular protein, thereby changing their function. Phosphatase cleaves this signal (preventing the labeling of phosphate groups).
There are more than 200 phosphatases in cells involved in many different processes, so any drug must selectively target only the right one, otherwise it can cause serious side effects or kill cells.
Drugs that target specific kinases (such as anticancer drugs) have been developed, but drugs that specifically target phosphatase are difficult—because the function of cleavage of the phosphate group is common to all phosphatases, so one Phosphatase administration inhibits hundreds of phosphatases and kills cells.
Dr. Bertolotti, who led the study, said: "For decades, because there is no way to selectively target phosphatases, scientists have lagged behind them with kinases, which has led them to be considered non-pharmaceutical. The new system is only a preliminary study, but we hope that the cracking of related issues will promote the in-depth study of phosphatase and drug development."
"Targeting phosphatase rather than kinases is like aiming at the brakes on cell signals rather than accelerators. By inhibiting phosphatase, we extend the signal events that have been activated, which is expected to be more safe to specifically change cells. Signal and help create new drugs with fewer side effects."
Huntingtin protein (green) accumulated in the cells from the brains of mice given a placebo. Credit: Krzyzosiak et al./ Cell
Huntington's disease patient gospel
The researchers then succeeded in identifying a molecule that showed promise in a mouse model of Huntington's disease when identifying the system.
Huntington's disease, also known as Huntington's disease (HD), is a neurodegenerative disease in which patients generally develop from middle age to physical, cognitive, and mental symptoms. The clinical symptoms are complex and variable, and the patient's condition is progressively worse, usually dying after 15 to 20 years of onset. On May 11, 2018, the National Health and Wellness Committee and other five departments jointly developed the "First Uncommon Diseases Catalogue", which was included in Huntington's disease.
Huntington's disease, like Alzheimer's disease and Parkinson's disease, is characterized by a misfolded protein that accumulates in brain cells. Researchers hope to slow down the production of cellular proteins to ensure that their "quality control machinery" has greater ability to eliminate misfolded proteins.
In this study, they aimed to slow down intracellular protein production by targeting a specific phosphatase, PPP1R15B. Using the new drug discovery platform, they found a molecule called rapin called Raphin1.
When the researchers tested Raphin1 in a mouse model of Huntington's disease, they found that Raphin1 could enter the brain, thereby reducing the accumulation of disease-associated misfolded proteins in neurons.
It should be pointed out that scientists emphasize that this is an early study and more work needs to be done to test whether the drug is safe or effective for the human body.
"Huntington's disease is a hereditary disease, and early genetic diagnosis can provide us with hope for treatment to target the disease before it occurs. Our approach is unique in manipulating cells to slow down normal function and provide clearance to cells. Huntington's unique opportunity to misfold proteins. However, it will take several years for us to know if this method is effective and safe for humans," Dr. Bertolotti concluded.
Reference materials:
1)New system can identify drugs to target 'undruggable' enzymes critical in many diseases
Original title: Cell breakthrough results! Cambridge scientist "Zhizhi" phosphatase for the benefit of rare patients
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