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Journal of Lipid Research, Vol. 49, 1595-1599, July 2008
Errata. PCSK9 function and physiology1
* Department of Molecular Biology, Genentech, South San Francisco, CA 1 See referenced articles, J. Lipid Res. 2008, 49: 1303–1311 and 1333–1343. Supported by NIH grants U01 HL66621 and R01 HL087228 (to SGY). Conflict of interest disclosures: Dr. Andrew Peterson is an employee of Genentech, a pharmaceutical and biotechnology company. Dr. Stephen G. Young is an employee of UCLA but periodically consults for Genentech and Isis Pharmaceuticals.
2 To whom correspondence should be addressed. e-mail: sgyoung{at}mednet.ucla.edu (S.G.Y) or peterson.andrew{at}gene.com (A.S.P)
PCSK9 has exploded onto center stage of plasma cholesterol metabolism, raising hopes for a new strategy to treat hypercholesterolemia. PCSK9 in a plasma protein that triggers increased degradation of the LDL receptor. Gain-of-function mutations in PCSK9 reduce LDL receptor levels in the liver, resulting in high levels of LDL cholesterol in the plasma and increased susceptibility to coronary heart disease. Loss-of-function mutations lead to higher levels of the LDL receptor, lower LDL cholesterol levels, and protection from coronary heart disease. Two papers in this issue of the Journal of Lipid Research exemplify the rapid pace of progress in understanding PCSK9 molecular interactions and physiology. Dr. Shilpa Pandit and coworkers from Merck Research Laboratories describe the functional basis for the hypercholesterolemia associated with gain-of-function missense mutations in PCSK9. Dr. Jay Horton's group at UT Southwestern describe the kinetics and metabolism of PCSK9 and the impact of PCSK9 on LDL receptors in the liver and adrenal gland.
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