Proprotein Convertase Subtilisin Kexin9 (PCSK9): A Novel Target For Cholesterol Regulation

Basak, Ajoy; Palmer-Smith, Heather; Mishra, Prashant

doi:10.2174/092986612800494020

Cited by 6 publications

(3 citation statements)

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“…The microeffects of many other genes relating to CAD development have yet to be fully understood (i.e., matrix metalloproteinase-9 gene-1562C>T polymorphism, TGF- β 1 gene−509C/T Polymorphism) ( 33 , 34 ). PCSK9 gene D129G, S127R, R496W, and R218S polymorphisms also influence the PCSK9 activity and CAD susceptibility ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

PCSK9 Gene E670G Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis of 5,484 Subjects

Wang

Yang

et al. 2020

Front. Cardiovasc. Med.

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Section: Discussionmentioning

confidence: 99%

PCSK9 Gene E670G Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis of 5,484 Subjects

Wang

Yang

et al. 2020

Front. Cardiovasc. Med.

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“…These observations unleashed a frantic investigation of the biochemistry, cell biology, genetics and pharmacology of this enzyme. Findings have been regularly summed up and updated in a continuous stream of review articles, written from varying perspectives and with differing emphasis …”

Section: Introductionmentioning

confidence: 99%

Proprotein Convertases Subtilisin/Kexin Type 9, an enzyme turned escort protein: Hepatic and extra hepatic functions (第9型前蛋白转换酶—枯草溶菌素/蛋白酶K，一种酶转变的护送蛋白：在肝脏与肝外的功能)

Mbikay

Mayne

Chrétien

2013

Journal of Diabetes

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Proprotein Convertases Subtilisin/Kexin Type 9 (PCSK9) is a serine endoproteinase. Biosynthesized as a zymogen, it cleaves itself once, and then turns into an escort protein for transmembrane proteins, leading them into lysosomes for degradation. It is primarily produced and secreted by the liver. It attaches to the low-density lipoprotein receptor (LDLR) at the surface of hepatocytes and, after co-endocytosis, directs it into lysosomes where it is degraded. By downregulating LDLR, PCSK9 reduces hepatic clearance of LDL-cholesterol. Inborn or induced increase of this function causes hypercholesterolemia; its decrease causes hypocholesterolemia. This has been experimentally demonstrated ex vivo and in vivo, and corroborated by epidemiological studies associating PCSK9 genetic variations with plasma cholesterol levels. PCSK9 is now a proven target for inactivation in the treatment of hypercholesterolemia and associated atherosclerosis. However, it is still uncertain whether its severe or complete inactivation, combined with other predispositions, will be without undesirable side-effects. Some experimental data suggest that PCSK9 could contribute positively to the physiology of non-hepatic cells such as pancreatic islets β cells, adipocytes and macrophages, protecting them from excessive lipid uptake, in an endocrine, autocrine, or paracrine manner. Genetic variations that attenuate PCSK9 anti-LDLR activity are common in human populations. Their evolutionary significance still needs to be evaluated on the background of environmental pressures, such as infectious diseases, cold weather and famine, which have threatened survival and reproduction in the course of human prehistory and history.

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“…Those findings show that PCSK9 might exist in critical stages of neuron synthesis, immigration, differentiation of neural cells. PCSK9 surge among primary neuronal cultures increases the variation of cortical neurons (28). Another study had revealed that PCSK9 is found in human CSF (29).…”

Section: Discussionmentioning

confidence: 97%

Pilot Study: Exploring PCSK9 in Maternal Serum as Potential Noninvasive Biomarker for Neural Tube Defects

Shaker,

Zaki,

Shalabi

2022

International Journal of Women’s Health and Reproduction Scienc

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Objectives: Neural tube defects (NTDs) are caused by inadequate closing of the neural tube. Alpha-fetoprotein has limitations due to its poor sensitivity and specificity in NTD detection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) appears to have an escalating role in neurogenesis. This study aimed to evaluate the two forms of PCSK9 (Mature PCSK9 and furin cleaved) circulating in NTD maternal sera as a potential novel non-invasive biochemical marker for prenatal screening of NTDs. Materials and Methods: In this case-control study, the presence of PCSK9 in serum samples of 30 pregnant women with current NTD fetuses (case group) and 30 pregnant women with a healthy singleton pregnancy (control group) was evaluated by Western blot analysis followed by the immuno-precipitation approach. Results: Median of mature PCSK9/furin ratio among the case group was 0.92 (0.05-2.54) versus 1.29 (0.19-6.62) among the control group (P = 0.02). Receiver operating characteristic curve analysis for mature PCSK9/furin ratio displayed a sensitivity and specificity equal to 63.3%. Conclusions: The ratio of mature PCSK9 to furin cleaved form was significantly reduced among women with current NTD fetuses compared to women having healthy pregnancies. This ratio can be a potential original biochemical marker in the non-invasive prenatal screening of NTDs.

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Proprotein Convertase Subtilisin Kexin9 (PCSK9): A Novel Target For Cholesterol Regulation

Cited by 6 publications

References 0 publications

PCSK9 Gene E670G Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis of 5,484 Subjects

PCSK9 Gene E670G Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis of 5,484 Subjects

Proprotein Convertases Subtilisin/Kexin Type 9, an enzyme turned escort protein: Hepatic and extra hepatic functions (第9型前蛋白转换酶—枯草溶菌素/蛋白酶K，一种酶转变的护送蛋白：在肝脏与肝外的功能)

Pilot Study: Exploring PCSK9 in Maternal Serum as Potential Noninvasive Biomarker for Neural Tube Defects

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