Researchers find new targets for lowering cholesterol
March 28, 2017 Source: Bio Valley
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)];In a new study published in Biochemical Pharmacology, researchers at St. Louis University examined a method by which a nuclear receptor called REV-ERB regulates cholesterol metabolism. Their findings suggest that drugs that target this nuclear receptor can lower the level of low-density lipoprotein (LDL) cholesterol in animal models.
Dr. Thomas Burris, Ph.D., head of the Department of Pharmacology and Physiology at the University of St. Louis, studied the nuclear receptor signaling of cells, which is the cellular signaling system behind many physiological processes in the body. He discovered natural hormones that regulate nuclear receptors and synthesized a compound that targets these receptors in order to develop drugs for disease treatment. One of these receptors is REV-ERB, a protein that plays multiple roles. Previously, Burris and colleagues have studied its role in regulating mammalian circadian clocks. To investigate the association of nuclear receptors with diabetes and obesity, Burris and colleagues used the $1362032 fund from the US Department of Defense to study the role of REV-ERB in regulating cholesterol metabolism.
Cholesterol is one of the essential components of cell membranes. Atherosclerosis is caused by a disorder of cholesterol metabolism. Drugs like statins can lower LDL cholesterol levels and the risk of atherosclerosis, but they are not effective for everyone, and some patients discontinue because of side effects. Therefore, new cholesterol-lowering drugs are urgently needed.
Nuclear receptors can regulate physiological processes such as growth, development, and metabolic homeostasis. REV-ERB is one of the nuclear receptors that can limit the transcription of target genes by binding to specific DNA sequences. Studies over the past few decades have shown that REV-ERB plays an important role in metabolic pathways. Past data suggest that REV-ERB deficiency disrupts lipid metabolism, and both LDL and total cholesterol levels in mice lacking REV-ERB are significantly increased. Similarly, in a previous study by Burris, he found that REV-ERB has the effect of inhibiting several cholesterol-related enzyme genes, and activation of REV-ERB by drugs can lead to further inhibition of these genes, which is associated with decreased cholesterol levels.
The results of this new study further reveal how REV-ERB directly or indirectly regulates cholesterol metabolism, suggesting that targeting REV-ERB may be an effective method for inhibiting LDL cholesterol levels in the clinic.
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