PURPOSE OF REVIEW: The purpose of this review is to highlight the recent findings of one of the most promising therapeutic targets in LDL cholesterol (LDL-C) management, proprotein convertase subtilisin/kexin type 9 (PCSK9). RECENT FINDINGS: Endoplasmic reticulum cargo receptor, surfeit locus protein 4 interacts with PCSK9 and regulates its exit from endoplasmic reticulum and its secretion. Once secreted, PCSK9 binds to heparin sulfate proteoglycans on the hepatocyte surface and this binding is required for PCSK9-LDL receptor (LDLR) complex formation and LDLR degradation. Posttranscriptionally, recent work has shown that PCSK9 gets degraded in lysosomes by activation of the glucagon receptor signaling, providing more data on the hormonal regulation of PCSK9. Finally, human studies with PCSK9 inhibitors offered more evidence on their benefits and safe use. SUMMARY: Recent work on the regulation of PCSK9 has enhanced our understanding of its biology, which may provide important information for future PCSK9-based therapies.
PURPOSE OF REVIEW: The purpose of this review is to highlight the recent findings of one of the most promising therapeutic targets in LDL cholesterol (LDL-C) management, proprotein convertase subtilisin/kexin type 9 (PCSK9). RECENT FINDINGS: Endoplasmic reticulum cargo receptor, surfeit locus protein 4 interacts with PCSK9 and regulates its exit from endoplasmic reticulum and its secretion. Once secreted, PCSK9 binds to heparin sulfate proteoglycans on the hepatocyte surface and this binding is required for PCSK9-LDL receptor (LDLR) complex formation and LDLR degradation. Posttranscriptionally, recent work has shown that PCSK9 gets degraded in lysosomes by activation of the glucagon receptor signaling, providing more data on the hormonal regulation of PCSK9. Finally, human studies with PCSK9 inhibitors offered more evidence on their benefits and safe use. SUMMARY: Recent work on the regulation of PCSK9 has enhanced our understanding of its biology, which may provide important information for future PCSK9-based therapies.
Authors: Robert P Giugliano; François Mach; Kenton Zavitz; Christopher Kurtz; Kyungah Im; Estella Kanevsky; Jingjing Schneider; Huei Wang; Anthony Keech; Terje R Pedersen; Marc S Sabatine; Peter S Sever; Jennifer G Robinson; Narimon Honarpour; Scott M Wasserman; Brian R Ott Journal: N Engl J Med Date: 2017-08-17 Impact factor: 91.245
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Authors: Brian A Ference; Jennifer G Robinson; Robert D Brook; Alberico L Catapano; M John Chapman; David R Neff; Szilard Voros; Robert P Giugliano; George Davey Smith; Sergio Fazio; Marc S Sabatine Journal: N Engl J Med Date: 2016-12-01 Impact factor: 91.245
Authors: Sokratis A Apostolidis; Amrita Sarkar; Heather M Giannini; Rishi R Goel; Divij Mathew; Aae Suzuki; Amy E Baxter; Allison R Greenplate; Cécile Alanio; Mohamed Abdel-Hakeem; Derek A Oldridge; Josephine Giles; Jennifer E Wu; Zeyu Chen; Yinghui Jane Huang; Ajinkya Pattekar; Sasikanth Manne; Oliva Kuthuru; Jeanette Dougherty; Brittany Weiderhold; Ariel R Weisman; Caroline A G Ittner; Sigrid Gouma; Debora Dunbar; Ian Frank; Alexander C Huang; Laura A Vella; John P Reilly; Scott E Hensley; Lubica Rauova; Liang Zhao; Nuala J Meyer; Mortimer Poncz; Charles S Abrams; E John Wherry Journal: bioRxiv Date: 2021-05-03
Authors: Sokratis A Apostolidis; Amrita Sarkar; Heather M Giannini; Rishi R Goel; Divij Mathew; Aae Suzuki; Amy E Baxter; Allison R Greenplate; Cécile Alanio; Mohamed Abdel-Hakeem; Derek A Oldridge; Josephine R Giles; Jennifer E Wu; Zeyu Chen; Yinghui Jane Huang; Jonathan Belman; Ajinkya Pattekar; Sasikanth Manne; Oliva Kuthuru; Jeanette Dougherty; Brittany Weiderhold; Ariel R Weisman; Caroline A G Ittner; Sigrid Gouma; Debora Dunbar; Ian Frank; Alexander C Huang; Laura A Vella; John P Reilly; Scott E Hensley; Lubica Rauova; Liang Zhao; Nuala J Meyer; Mortimer Poncz; Charles S Abrams; E John Wherry Journal: Front Immunol Date: 2022-03-03 Impact factor: 8.786
Authors: Jorge L Rodriguez-Gil; Laura L Baxter; Dawn E Watkins-Chow; Nicholas L Johnson; Cristin D Davidson; Steven R Carlson; Arturo A Incao; Kerri L Wallom; Nicole Y Farhat; Frances M Platt; Ryan K Dale; Forbes D Porter; William J Pavan Journal: Hum Mol Genet Date: 2021-11-30 Impact factor: 5.121