Zelcer identified a gene that influences the breakdown of these receptors. 'The gene works like a traffic controller,' he explains. 'As soon as there is too much cholesterol in the cell, it sends the LDL receptors to the lysosome, the waste processing centre of the cell. They are broken down there, so that the cell absorbs less cholesterol and the balance is restored.'

IDOL

Zelcer named the cell IDOL, which stands for Inducible Degrader Of the LDLR. This cell repairs the internal balance. But the same degradation mechanism that maintains the internal balance could well be a factor that prevents statins from working optimally: namely allowing LDL to be removed from the blood by cells. Zelcer: There are indications that this could be the case, so we have studied what happens if we switch off the IDOL.' Raised receptor level They managed to do this successfully, both in mice cells and in human cells in a test tube. As soon as the researchers inactived the IDOL, or reduced the amount, the level of the LDL receptor rose, so that the cell was able to absorb more LDL cholesterol. Zelcer is now researching wh ether influencing IDOL might lead to a new cholesterol-reducing therapy that complements the working of statins.

Full bibliographic information: LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor Noam Zelcer, Cynthia Hong, Rima Boyadjian, Peter Tontonoz Science Express 11 June 2009

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