A novel breakthrough advance in fighting low-density lipoprotein (LDL) or “bad” cholesterol in the body has been announced by investigators from the University of Leicester and University of California Los Angeles (UCLA).
The universities have filed two patents in order to develop targeted medications designed to lower levels of LDL. LDL is frequently associated to medical conditions, such as stroke, heart disease and clogged arteries.
Cells in the liver generate an LDL receptor that attaches to “bad” cholesterol and eliminates it from the blood, thus reducing cholesterol levels. Although, the goal of these receptors can sometimes be obstructed.
According to the researchers, an enzyme called IDOL plays a vital and specific role in the ability of the receptor to attach with LDL. Targeting IDOL with medications would help the receptors to lower cholesterol levels in humans.
Professor John Schwabe, Head of Biochemistry at the University of Leicester, explained:
“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.”
The research by Prof John Schwabe, Dr Ben Goult and Dr Louise Fairall at the University of Leicester together with the University of California Los Angeles (UCLA), was published in Genes & Development as well as the Proceeds of the National Academy of Science (PNAS). The Wellcome Trust funded the UK research, while the US research received funding from NIH and the National Heart Foundation of Australia Overseas Fellowship.
The study published in Genes & Development reveals the first atomic structural information on IDOL and identified the E2 ligase. The LDL receptor is degraded by UBE2D, which works with IDOL.
In the second study published in PNAS, the researchers explain in detail the molecular foundation for the powerful specificity of IDOL for the “bad” cholesterol receptor.
Prof. Schwabe, stated:
“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.”
Written by: Grace Rattue