02:59pm Friday 15 December 2017

New advance announced in reducing 'bad' cholesterol

Illustration of how IDOL binds to the tails of LDL receptors, ultimately causing them to be degraded and hence preventing them from removing ‘bad’ cholesterol from the blood.

Graphic illustration available from pt91@le.ac.uk

Scientists from the University of Leicester and the University of California Los Angeles (UCLA) have announced a major advance towards developing drugs to tackle dangerous, or ‘bad’, cholesterol in the body.

They have filed two patents for developing targeted drugs that would act as a catalyst for lowering levels of ‘bad’ cholesterol.

Two research papers published by the academics enhance the understanding of the regulation of low-density lipoprotein (LDL) or “bad” cholesterol.

LDL, the so-called “bad” cholesterol, is often linked to medical problems like heart disease, stroke and clogged arteries.

In the body, cells in the liver produce an LDL receptor that binds LDL and removes it from the blood, thereby lowering cholesterol levels.

The scientists have characterised an enzyme called IDOL that plays a key role in regulating the amount of LDL receptor available to bind with ‘bad’ cholesterol.  Therefore targeting the enzyme with drugs could increase the levels of LDL receptors present, thus lowering circulating cholesterol in humans.

Professor John Schwabe, Head of Biochemistry at the University of Leicester, said: “Development of a drug that interferes with IDOL’s activity could help lower levels of LDL.  Our research has greatly enhanced our understanding of this important process.”

Prof John Schwabe, Dr Ben Goult and Dr Louise Fairall at the University of Leicester in collaboration with the University of California Los Angeles (UCLA) published their research in the top research journals: Genes & Development and the Proceedings of the National Academy of Science (PNAS). The research was funded by The Wellcome Trust, the NIH and the Howard Hughes Medical Institute.

The study published in Genes & Development announced the first atomic structural information on IDOL and identified the E2 ligase, UBE2D that works with IDOL to degrade the LDL receptor.

In the second research article published in PNAS, the team elucidated the molecular basis for the stringent specificity of IDOL for the LDL receptor.

Professor Schwabe added: “Remarkably, IDOL only targets three proteins for degradation (all lipoprotein receptors) and this research paper greatly enhances our understanding of this specificity and identifies key residues involved in mediating this interaction.”

“A potential future drug that targets IDOL could be prescribed in conjunction with statin drugs, which also cut cholesterol levels by increasing production of the LDL receptor and these two studies make considerable headway towards this.”

The universities have filed 2 patents related to the research findings.

Both research papers are available online at:

http://genesdev.cshlp.org/content/25/12/1262.long

http://www.pnas.org/content/early/2011/11/21/1111589108.long

Full PDF versions of the papers can be accessed for free through the website.

Ends

For more information contact:

Prof. John Schwabe, University of Leicester: 0116 229 7030

Email js336@leicester.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk


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