Abstract：
:Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
He NY,Li Q,Wu CY,Ren Z,Gao Y,Pan LH,Wang MM,Wen HY,Jiang ZS,Tang ZH,Liu LSdoi
10.1038/aps.2016.134subject
Has Abstractpub_date
2017-03-01 00:00:00pages
301-311issue
3eissn
1671-4083issn
1745-7254pii
aps2016134journal_volume
38pub_type
杂志文章,评审abstract：:Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a prot...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0462-y
更新日期：2020-10-01 00:00:00
abstract：:Brain and eye tissues are subject to a reduced version of immune surveillance, which has evolved to protect the particularly sensitive tissues from accidental bystander damage created by regular inflammatory responses. Yet, there are autoimmune diseases in both organs. This review discusses the nature of immune reacti...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2010.149
更新日期：2010-09-01 00:00:00
abstract：AIM:To study the alterations of myocardial taurine transport function, taurine transporter (TAUT), and cysteine sulfinate decarboxylase (CSD) mRNA as well as effect of exogenous taurine in rats with isoproterenol (ISO)-induced cardiomegaly. METHODS:[3H]-Taurine uptake and release on myocardium were determined. Binding...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-10-01 00:00:00
abstract：:The pandemic of coronavirus disease 2019 (COVID-19) and its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the greatest current threat to global public health. The highly infectious SARS-CoV-2 virus primarily attacks pulmonary tissues and impairs gas exchange leading to acute respir...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/s41401-020-00554-8
更新日期：2020-12-01 00:00:00
abstract：AIM:To examine the effect of tachykinins on the ascending reflex pathway in rat small intestine, we used different selective neurokinin (NK) receptor antagonists (RA): a) NK1-RA: GR-82334 and CP-96.345, b) NK2-RA: MEN-10.376 and L-659.877. The aim was further to investigate the effect of substance P (SP) on the ascendi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-04-01 00:00:00
abstract：AIM:Extract of Hominis Placenta (HP) has been used in oriental medicine as an agent for improving physiological function. The present study was conducted to investigate whether HP treatment in an experimental sciatic nerve injury animal model produces growth-promoting effects on regenerating peripheral nerve fibers aft...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00252.x
更新日期：2006-01-01 00:00:00
abstract：AIM:To investigate whether total Panax notoginseng saponins (PNS) could protect endothelium of rabbit iliac artery against balloon endothelial denudation (BED) injury. METHODS:The morphology changes of the endothelium were observed with scanning electron microscope (SEM) and hematoxylin and eosin stain after BED of ra...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-09-01 00:00:00
abstract：AIM:To investigate the antidepressant-like effects of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-methoxyquinoxalin-2-carboxamide (6z) in acute and chronic murine models of depression. METHODS:5-HT3 receptor antagonism was examined in guinea pig ileum in vitro. A tail suspension test (TST) was used as...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2014.89
更新日期：2014-12-01 00:00:00
abstract：AIM:To investigate the expression of c-Met in peritoneal free cancer cells isolated from human gastric cancer ascites, and its relationship to peritoneal dissemination of gastric cancer. METHODS:Peritoneal free cancer cells (PFCCs) were isolated from ascites specimens of gastric cancer patients. c-Met expression in PF...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.205
更新日期：2012-04-01 00:00:00
abstract：AIM:To study the effect of gum mastic, a natural resin, on the proliferation of androgen-independent prostate cancer PC-3 cells, and further investigate the mechanisms involved in this regulatory system, taking nuclear factor kappaB (NF-kappaB) signal as the target. METHODS:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00536.x
更新日期：2007-03-01 00:00:00
abstract：AIM:The metabolites of naproxen produced by Cunninghamella species were isolated and identified, and further to compare the similarities between microbial transformation and mammalian metabolism. METHODS:Naproxen was transformed by three strains of Cunninghammella species (Cunninghamella blakeslesna AS 3.153, Cunningh...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2003-05-01 00:00:00
abstract：AIM:To investigate the inhibitory effect of the natural product Leukamenin F on liver fibrosis and explore its potential underlying mechanisms. METHODS:Carbon tetrachloride (CCl(4))-treated mouse model in vivo and in hepatic stellate cells (HSC) in vitro were used. The effect on CCl(4)-induced liver fibrosis was studi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.64
更新日期：2010-07-01 00:00:00
abstract：:Telomere shortening is associated with idiopathic pulmonary fibrosis (IPF), a high-morbidity and high-mortality lung disease of unknown etiology. However, the underlying mechanisms remain largely unclear. In this study, wild-type (WT) mice with normal telomeres and generation 3 (G3) or G2 telomerase RNA component (TER...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0007-9
更新日期：2018-11-01 00:00:00
abstract：AIM:To investigate the actions of the muscarinic agonist carbachol on glutamate-induced neurotoxicity in PC12 cells, and the underlying mechanisms. METHODS:PC12 cells were treated with different concentrations of glutamate for 24 or 48 h. The cell viability was measured using MTT assay, and the expression and activati...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.42
更新日期：2013-07-01 00:00:00
abstract：:Dry eye disease (DED) is a multifactorial disorder of the tears and ocular surface characterized by manifestations of dryness and irritation. Although the pathogenesis is not fully illuminated, it is recognized that inflammation has a prominent role in the development and deterioration of DED. β-aminoarteether maleate...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0484-5
更新日期：2020-08-03 00:00:00
abstract：:As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capaci...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/s41401-020-0415-5
更新日期：2020-07-01 00:00:00
abstract：AIM:To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS:Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were tre...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.133
更新日期：2014-01-01 00:00:00
abstract：AIM:To examine whether (-)-stepholidine (SPD) has a direct effect on the N-methyl- D-aspartic acid receptors (NMDAR) containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol (Hal) and clozapine (Cloz). METHODS:NMDAR was transiently expressed in human embryonic kidney 293 (...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00581.x
更新日期：2007-07-01 00:00:00
abstract：AIM:To investigate the effect of melittin (Mel) on papillary muscles of guinea pigs. METHODS:Contraction of papillary muscles were examined by conventional method and action potentials (AP) were recorded by standard glass microelectrode technique. RESULTS:Mel (0.5, 3 micromol/L) significantly increased the contractil...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-08-01 00:00:00
abstract：:Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, art...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2016.110
更新日期：2017-03-01 00:00:00
abstract：AIM:To determine whether ATP-sensitive potassium channels are altered in VSMC from arotas and mesenteric arteries of obese rat, and their association with obesity-triggered increase in blood pressure. METHODS:Obesity was induced by 24 weeks of high-fat diet feeding in male Sprague-Dawley rats. Control rats were fed wi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00810.x
更新日期：2008-10-01 00:00:00
abstract：AIM:The interaction of anthracycline anticancer drugs with chromatin, nucleosomes and histone H1 has been extensively studied. In the present study, for the first time, we have investigated the binding of anthracycline antibiotic, daunomycin, to free and cross-linked thymus core histones (CL-core) in solution and in th...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00542.x
更新日期：2007-05-01 00:00:00
abstract：AIM:To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I(Ca,L)) in rat ventricular myocytes. METHODS:The whole-cell patch-clamp techniques were used to record I(Ca,L) in rat ventricular myocytes. RESULTS:Hyposmotic challenge(∼220 mosmol/L) induced biphasic c...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.112
更新日期：2010-11-01 00:00:00
abstract：AIM:In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions. RE...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00614.x
更新日期：2007-10-01 00:00:00
abstract：:Diabetic retinopathy (DR) is a common complication of diabetes and has been recognized as the leading cause of blindness in adults. Several interrelated molecular pathways are involved in the development of DR. Microvesicles (MVs) are cell membrane vesicles, which carry many biologic molecules, such as mRNAs, microRNA...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2017.77
更新日期：2018-01-01 00:00:00
abstract：AIM:To study the protective effect of the polypeptide isolated from Chlamys farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS:Enzymes and malondialdehyde (MDA) were determined by biochemical methods; the expressions of Bcl-2 protein and NOS protein were examined by immunohistochemical technique. Th...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：AIM:To investigate the effects of 3,4,4'-trihydroxy-trans-stilbene (3,4,4'-THS), an analogue of resveratrol, on human non-small-cell lung cancer (NSCLC) cells in vitro. METHODS:Cell viability of NSCLC A549 cells was determined by MTT assay. Cell apoptosis was evaluated using flow cytometry and TUNEL assay. Cell necros...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2015.46
更新日期：2015-10-01 00:00:00
abstract：AIM:To study the effect of new antihepatitis drug, bicyclol, on the metabolism and hepatotoxicity of aflatoxin B1 (AFB1) in rats. METHODS:Rats were given bicyclol 300 mg/kg/d ig for 3 d and then injected ip with AFB1 1.5 mg/kg. Liver damages were examined 16 h after ip AFB1. The in vitro metabolism of AFB1 by bicyclol...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-10-01 00:00:00
abstract：:In drug design and discovery, binding affinity and selectivity are two basic properties of a drug candidate. Opioid receptors (ORs) are the main targets of strong analgesics. Like some other class A members of G-protein-coupled receptors (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of bindi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.132
更新日期：2018-03-01 00:00:00
abstract：AIM:The substrate cocktail is frequently used to evaluate cytochrome P450 (CYP) enzyme-mediated drug interactions and potential interactions among the probe substrates. Here, we re-optimized the substrate cocktail method to increase the reliability and accuracy of screening for candidate compounds and expanded the meth...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2016.10
更新日期：2016-05-01 00:00:00
