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The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

IDOL, inducible degrader of low-density lipoprotein receptor, serves as a potential therapeutic target for dyslipidemia

Zhang, Cai-ping, Tian, Ying, Zhang, Min, Tuo, Qin-hui, Chen, Jian-xiong, Liao, Duan-fang·2016·Medical Hypotheses
DOI 10.1016/j.mehy.2015.11.010
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Abstract

Low-density lipoprotein cholesterol (LDL-C) is the hall marker for the atherosclerotic cardiovascular disease (ASCVD). It has been shown that over 70% of circulating LDL-C is metabolized through binding and activation of hepatic LDL receptor (LDLR). Genetic LDLR mutations cause hypercholesterolemia in the patients. Therefore, elevation of LDLR levels is beneficial for the treatment of dyslipidemia. LDLR expression is regulated by the SREBP2/PCSK9 pathways. Targeting SREBP2/PCSK9 pathways by statins and human monoclonal PCSK9 antibody has been shown to reduce the progression of ASVCD. Recent studies identified that inducible degrader of LDLR (IDOL) is a novel regulator of LDLR. IDOL is an E3-ubiquitin ligase regulated via liver X receptors (LXRs) binding to the upstream of translation start site of IDOL. IDOL modulates LDLR distribution through ubiquitination and degradation of LDLR in lysosomes. Genome-wide association studies (GWAS) have revealed that the nonsynonymous substitution rs9370867 of IDOL probably contributes to the variability of circulating LDL levels. Recently studies also demonstrated that IDOL influences PCSK9 expression in a LDLR/SREBP2-dependent manner. Based upon these novel findings, we hypothesize that IDOL and PCSK9 would have a synergistic effect on LDLR distribution. Specifically, loss of IDOL increases LDLR distribution in the hepatic cell, and subsequently reduces serum LDL-C levels in dyslipidemic patients. IDOL might be a potential therapeutic tar…

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Research works printed but not linked: 29

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Metadata

Authors
Zhang, C.-P., Tian, Y., Zhang, M., Tuo, Q.-H., Chen, J.-X., & Liao, D.-F.
Venue
Medical Hypotheses
Publisher
Elsevier BV
Published
2016-01
Volume
86
Pages
138-142
ISSN
0306-9877
DOI
10.1016/j.mehy.2015.11.010
Cited by
28
References
6
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Funders
  • National Nature Science Fund of China (81173047, 31371161)
  • Nature Science Fund of Hunan province (15JJ6077, 14JJ1024, 14JJ3104)
  • Pharmaceutical Science key discipline in Hunan province

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