Progranulin: a growth factor, a novel TNFR ligand and a drug target.


:Progranulin (PGRN) is abundantly expressed in epithelial cells, immune cells, neurons, and chondrocytes, and reportedly contributes to tumorigenesis. PGRN is a crucial mediator of wound healing and tissue repair. PGRN also functions as a neurotrophic factor and mutations in the PGRN gene resulting in partial loss of the PGRN protein cause frontotemporal dementia. PGRN has been found to be a novel chondrogenic growth factor and to play an important role in cartilage development and inflammatory arthritis. Although research has shown that PGRN exhibits anti-inflammatory properties, the details about the exact molecular pathway of such effects, and, in particular, the PGRN binding receptor, have not been identified so far. Recently, researchers have shown that PGRN binds to tumor necrosis factor (TNF)-receptors (TNFR), interfering with the interaction between TNFα and TNFR. They further demonstrated that mice deficient in PGRN are susceptible to collagen-induced arthritis, an experimental model of rheumatoid arthritis, and that administration of PGRN reversed the arthritic process. An engineered protein made of three PGRN fragments (Atsttrin), displayed selective TNFR binding and was more active than natural PGRN. Both PGRN and Atsttrin prevented inflammation in various arthritis mouse models and inhibited TNFα-induced intracellular signaling pathways. Thus, PGRN is a key regulator of inflammation and it may mediate its anti-inflammatory effects, at least in part, by blocking TNF binding to its receptors. As we discuss here, TNFR-based interventions may both stimulate and suppress the growth of cancer cells, and the same may be true in analogy for Atsttrin as a new player.


Pharmacol Ther


Liu CJ,Bosch X




Has Abstract


2012-01-01 00:00:00














  • Alteration of nitric oxide-mediated blood flow regulation in diabetes mellitus.

    abstract::Nitric oxide (NO) formed via endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) plays crucial roles in the regulation of blood flow through vasodilatation and decreased vascular resistance in various organs and tissues. NO derived from eNOS also contributes to the inhibition of platelet aggregation, adhesi...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Toda N,Imamura T,Okamura T

    更新日期:2010-09-01 00:00:00

  • Therapeutic options for 5-lipoxygenase inhibitors.

    abstract::5-Lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) into leukotriene (LT) A(4) and 5-hydroperoxyeicosatetraenoic acid. LTA(4) can then be converted into LTB(4) by LTA(4) hydrolase or into LTC(4) by LTC(4) synthase and the LTC(4) synthase isoenzymes MGST2 and MGST3. LTB(4) is a potent chemoattractan...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Werz O,Steinhilber D

    更新日期:2006-12-01 00:00:00

  • Peroxisome proliferator-activated receptors and inflammation.

    abstract::Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors family. PPARs are a family of 3 ligand-activated transcription factors: PPARalpha (NR1C1), PPARbeta/delta (NUC1; NR1C2), and PPARgamma (NR1C3). PPARalpha, -beta/delta, and -gamma are encoded by different genes but show sub...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Moraes LA,Piqueras L,Bishop-Bailey D

    更新日期:2006-06-01 00:00:00

  • In utero drug therapy.

    abstract::Drug therapy directed toward the fetus would be intended for either treating a fetal disorder or improving the capacity for later intrauterine or postnatal adaptation. Most reported trials involve single cases or small numbers of fetuses receiving the drug transplacentally after the first trimester, but before attaini...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Rayburn WF,Payne GG Jr

    更新日期:1993-01-01 00:00:00

  • Measurement of sister chromatid exchanges and their relationship to DNA damage, repair and cell killing.

    abstract::We have concentrated on how SCE is measured, how it correlates with other measures of cellular damage, and how SCE can be used as a tool to study cell cycle kinetics. We have not discussed the biological significance of SCEs, i.e. why they occur spontaneously, and what role, if any, in cellular preservation they play....

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Deen DF,Morgan WF,Tofilon PJ,Barcellos-Hoff MH

    更新日期:1989-01-01 00:00:00

  • The role of the renin-angiotensin system in thoracic aortic aneurysms: clinical implications.

    abstract::Thoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with β-adrenoceptor blockers. Increasing evidence supports a role for the renin-angiotensin system (RAS) in ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Moltzer E,Essers J,van Esch JH,Roos-Hesselink JW,Danser AH

    更新日期:2011-07-01 00:00:00

  • Cyclic nucleotide phosphodiesterases: pharmacology, biochemistry and function.

    abstract::This article is a review of cyclic nucleotide phosphodiesterase(s) (CN PDE) from the point of view of the relationships between the newer aspects of the complex enzymology of CN PDE and recent major advances in CN PDE pharmacology. A consolidation of isozyme nomenclature to the proposed family designations is recommen...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Thompson WJ

    更新日期:1991-01-01 00:00:00

  • Atypical behavioural effects of lorazepam: clues to the design of novel therapies?

    abstract::Aside from their pharmacokinetic properties, e.g. their speed of action and the duration of residual effects, benzodiazepines are still considered as equivalent in terms of their effects on cognition. Here we review evidence suggesting that certain benzodiazepines, especially lorazepam, differ in a number of respects,...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Giersch A,Boucart M,Elliott M,Vidailhet P

    更新日期:2010-04-01 00:00:00

  • Drug uptake transporters in antiretroviral therapy.

    abstract::Current treatment of human immunodeficiency virus-1 (HIV-1) infection is effective, although it does not permanently suppress viral replication in all patients. Viral persistence, drug toxicity, and antiretroviral resistance are challenging barriers to successful treatment of HIV-1 infection. It has become increasingl...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Minuesa G,Huber-Ruano I,Pastor-Anglada M,Koepsell H,Clotet B,Martinez-Picado J

    更新日期:2011-12-01 00:00:00

  • Benzodiazepines, anxiety and immunity.

    abstract::Experimental and clinical studies suggest that the central and peripheral benzodiazepine (BDZ) receptors together with their ligands form the molecular basis of a novel regulatory network that contributes to the effects of anxiety on immune status. The peripheral-type receptors located on phagocytes and glial cells ap...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Zavala F

    更新日期:1997-09-01 00:00:00

  • Dietary manipulation of platelet function.

    abstract::Activated platelets contribute to plaque formation within blood vessels in the early and late stages of atherogenesis, and therefore they have been proposed as risk factor for cardiovascular disease. Anti-platelet drugs, such as aspirin, are now the most prescribed pharmacological treatment in Europe. Certain dietary ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Bachmair EM,Ostertag LM,Zhang X,de Roos B

    更新日期:2014-11-01 00:00:00

  • Role of Ca(2+) and vitamin D in the prevention and treatment of osteoporosis.

    abstract::Osteoporosis is defined as a progressive systemic skeletal disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The clinical relevance of osteoporosis derives from the fractures that it produces. More th...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Rodríguez-Martínez MA,García-Cohen EC

    更新日期:2002-01-01 00:00:00

  • Possibility of a rebound phenomenon following antiplatelet therapy withdrawal: a look at the clinical and pharmacological evidence.

    abstract::The importance of regular administration of antiplatelet drugs in patients suffering from coronary artery disease stands on firm grounds, as large meta-analyses have shown these therapies to drastically reduce the risk of death. Although the current guidelines published jointly by the American Heart Association, the A...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Lordkipanidzé M,Diodati JG,Pharand C

    更新日期:2009-08-01 00:00:00

  • Therapeutic applications of ribozymes.

    abstract::The demonstration that RNA can be cleaved by cis or trans ribozymes (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Since their discovery in the 1980s, the biochemistry and conserved sequences of ribozymes have been well characterized. Ribozymes are effective modulators of gene expres...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Kijima H,Ishida H,Ohkawa T,Kashani-Sabet M,Scanlon KJ

    更新日期:1995-01-01 00:00:00

  • Targeting TRK family proteins in cancer.

    abstract::The tropomyosin receptor kinase (TRK) family includes TRKA, TRKB, and TRKC proteins, which are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Binding of neurotrophins to TRK proteins induces receptor dimerization, phosphorylation, and activation of the downstream signaling cascades via PI3K, RAS/MAPK/ERK, and ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Khotskaya YB,Holla VR,Farago AF,Mills Shaw KR,Meric-Bernstam F,Hong DS

    更新日期:2017-05-01 00:00:00

  • Nitrones as neuroprotective agents in cerebral ischemia, with particular reference to NXY-059.

    abstract::Stroke is a major clinical problem, and acute pharmacological intervention with neuroprotective agents has so far been unsuccessful. Recently, there has been considerable interest in the potential therapeutic benefit of nitrone-derived free radical trapping agents as neuroprotective agents. Nitrone compounds have been...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Green AR,Ashwood T,Odergren T,Jackson DM

    更新日期:2003-12-01 00:00:00

  • Myotoxicity of statins: Mechanism of action.

    abstract::Statins are effective drugs to reduce cardiovascular events secondary to dyslipidemia; however, they cause frequent undesirable side effects. The incidence of statin-induced myotoxicity (SIM) is presented by 7 to 29% of patients, depending upon the report. SIM may develop in presence of abnormally high concentrations ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: du Souich P,Roederer G,Dufour R

    更新日期:2017-07-01 00:00:00

  • Lorcaserin: A review of its preclinical and clinical pharmacology and therapeutic potential.

    abstract::The selective 5-HT2C receptor agonist lorcaserin, in conjunction with lifestyle modification, was approved by the FDA in 2012 for weight management. It has been marketed in the US as Belviq® since 2013. This article provides a review of the preclinical and clinical pharmacology of lorcaserin, including its pharmacokin...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Higgins GA,Fletcher PJ,Shanahan WR

    更新日期:2020-01-01 00:00:00

  • Endocrine pathology of estrogens: species differences.

    abstract::The clinical uses of estrogens are associated with serious adverse effects, so the experimental toxicology of these compounds is under continuous review. Structurally different estrogens have qualitatively similar effects in animals when given in amounts way above the rodent uterotrophic dose. Toxicity still tends, ho...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Hart JE

    更新日期:1990-01-01 00:00:00

  • The role of transporters in cellular heme and porphyrin homeostasis.

    abstract::Heme, a complex of iron and protoporphyrin IX (PPIX), senses and utilizes oxygen in nearly all living cells. It is an essential component of various hemoproteins, including those involved in oxygen transport and storage (hemoglobin, myoglobin), electron transfer, drug and steroid metabolism (cytochromes), and signal t...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Krishnamurthy P,Xie T,Schuetz JD

    更新日期:2007-06-01 00:00:00

  • Coronary microcirculation: physiology and pharmacology.

    abstract::Coronary microvessels play a pivotal role in determining the supply of oxygen and nutrients to the myocardium by regulating the coronary flow conductance and substance transport. Direct approaches analyzing the coronary microvessels have provided a large body of knowledge concerning the physiological and pharmacologic...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Komaru T,Kanatsuka H,Shirato K

    更新日期:2000-06-01 00:00:00

  • K(+) channels as therapeutic drug targets.

    abstract::K(+) channels play critical roles in a wide variety of physiological processes, including the regulation of heart rate, muscle contraction, neurotransmitter release, neuronal excitability, insulin secretion, epithelial electrolyte transport, cell volume regulation, and cell proliferation. As such, K(+) channels have b...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Wickenden A

    更新日期:2002-04-01 00:00:00

  • Challenges and achievements in the therapeutic modulation of aquaporin functionality.

    abstract::Aquaporin (AQP) water and solute channels have basic physiological functions throughout the human body. AQP-facilitated water permeability across cell membranes is required for rapid reabsorption of water from pre-urine in the kidneys and for sustained near isosmolar water fluxes e.g. in the brain, eyes, inner ear, an...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Beitz E,Golldack A,Rothert M,von Bülow J

    更新日期:2015-11-01 00:00:00

  • Small heat shock proteins in smooth muscle.

    abstract::The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Salinthone S,Tyagi M,Gerthoffer WT

    更新日期:2008-07-01 00:00:00

  • Pericytes for the treatment of orthopedic conditions.

    abstract::Pericytes and other perivascular stem cells are of growing interest in orthopedics and tissue engineering. Long regarded as simple regulators of angiogenesis and blood pressure, pericytes are now recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: James AW,Hindle P,Murray IR,West CC,Tawonsawatruk T,Shen J,Asatrian G,Zhang X,Nguyen V,Simpson AH,Ting K,Péault B,Soo C

    更新日期:2017-03-01 00:00:00

  • Preventing asthma exacerbations: what are the targets?

    abstract::Exacerbations of asthma are the main cause of asthma morbidity. They induce acute respiratory failure, and sometimes death. Two immunological signals acting in synergy are necessary for inducing asthma exacerbations. The first, triggered by allergens and/or unknown agents leads to the chronic Th2 inflammation characte...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Botturi K,Langelot M,Lair D,Pipet A,Pain M,Chesne J,Hassoun D,Lacoeuille Y,Cavaillès A,Magnan A

    更新日期:2011-07-01 00:00:00

  • Current status of data on cangrelor.

    abstract::P2Y12 receptor inhibition in addition to aspirin is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI). Despite advances in contemporary antithrombotic therapy, periprocedural thrombotic complications such as myocardial infarction ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Qamar A,Bhatt DL

    更新日期:2016-03-01 00:00:00

  • 30 years of dynorphins--new insights on their functions in neuropsychiatric diseases.

    abstract::Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain. Dynorphins are members of the opioid peptide family and preferentially bind to kappa opioid receptors. In line with their localizat...

    journal_title:Pharmacology & therapeutics

    pub_type: 历史文章,杂志文章,评审


    authors: Schwarzer C

    更新日期:2009-09-01 00:00:00

  • Overcoming drug resistance to receptor tyrosine kinase inhibitors: Learning from lung cancer.

    abstract::There are various receptor tyrosine kinase (TK)-targeted drugs that are currently used in the treatment of patients with non-small cell lung cancer (NSCLC). Among them, the epidermal growth factor receptor (EGFR) TK inhibitors (TKIs) are the most extensively studied. Receptor TKIs including EGFR TKIs have shown dramat...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Kuwano M,Sonoda K,Murakami Y,Watari K,Ono M

    更新日期:2016-05-01 00:00:00

  • Using animal models to develop therapeutics for Tourette Syndrome.

    abstract::The science of Tourette Syndrome (TS) is advancing at multiple levels of analysis and will be enhanced through the use of animal models. Particular challenges in the development of TS animal models reflect complex features of this disorder, including its waxing and waning course and its "invisible" sensory and psychic...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Swerdlow NR,Sutherland AN

    更新日期:2005-12-01 00:00:00