| PCSK9 as a therapeutic target of dyslipidemia. | |
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MedLine Citation:
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PMID: 19063703 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), which promotes degradation of hepatic low density lipoprotein receptor (LDLR), has a role in plasma cholesterol metabolism. Its gene is associated with the development of familial hypercholesterolemia. mRNA silencing or inhibition of PCSK9-induced degradation of LDLR may be used to treat this disease. OBJECTIVE/METHODS: To summarize approaches proposed to reduce the levels of PCSK9 and/or its activity. RESULTS/CONCLUSIONS: mRNA knockdown approaches include the use of antisense oligonucleotides either as soluble phosphorothioates or locked nucleic acids and lipidoid nanoparticles embedded with small interfering RNAs. Passive immunization is also an option. Other strategies include inhibition of the zymogen activation of proPCSK9, or the interaction of PCSK9 with the EGF-A domain of the LDLR. The N-terminal prosegment and the C-terminal Cys-His rich domain (CHRD), are alternative targets. Annexin A2 specifically binds the CHRD and inhibits PCSK9 function, and Annexin A2 peptide mimics could pave the way for the development of novel PCSK9-inhibitory compounds. |
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Authors:
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Nabil G Seidah |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Expert opinion on therapeutic targets Volume: 13 ISSN: 1744-7631 ISO Abbreviation: Expert Opin. Ther. Targets Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-09 Completed Date: 2009-03-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101127833 Medline TA: Expert Opin Ther Targets Country: England |
Other Details:
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Languages: eng Pagination: 19-28 Citation Subset: IM |
Affiliation:
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Clinical Research Institute of Montreal, Laboratory of Biochemical Neuroendocrinology, 110 Pine Ave West, Montreal, QC, H2W 1R7 Canada. seidahn@ircm.qc.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cysteine
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chemistry Dyslipidemias / enzymology* Histidine / chemistry Humans Models, Molecular Protein Conformation Serine Endopeptidases / chemistry, drug effects*, genetics |
| Chemical | |
Reg. No./Substance:
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52-90-4/Cysteine; 71-00-1/Histidine; EC 3.4.21.-/PCSK9 protein, human; EC 3.4.21.-/Serine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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