TSPO Finds NOX2 in Microglia for Redox Homeostasis.

Abstract:

:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial cells. Here, we identify a novel function of TSPO in microglia that is not associated with steroidogenesis. We propose that a TSPO interaction with NADPH oxidase (NOX2) links the generation of reactive oxygen species (ROS) to the induction of an antioxidant response to maintain redox homeostasis. This line of investigation may provide a greater understanding of TSPO glial cell biology, and the knowledge gained may prove beneficial in devising therapeutic strategies.

journal_name

Trends Pharmacol Sci

authors

Guilarte TR,Loth MK,Guariglia SR

doi

10.1016/j.tips.2016.02.008

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

334-343

issue

5

eissn

0165-6147

issn

1873-3735

pii

S0165-6147(16)00043-2

journal_volume

37

pub_type

杂志文章,评审
  • Pharmacological inhibitors of MAPK pathways.

    abstract::Mitogen-activated protein kinases [MAPKs, also called extracellular signal-regulated kinases (ERKs)] are constituents of numerous signal transduction pathways, and are activated by protein kinase cascades. Intense efforts are under way to develop and evaluate compounds that target components of MAPK pathways. In this ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)01865-4

    authors: English JM,Cobb MH

    更新日期:2002-01-01 00:00:00

  • A novel way to spread drug resistance in tumor cells: functional intercellular transfer of P-glycoprotein (ABCB1).

    abstract::Intercellular transfer of proteins is a mode of communication between cells that is crucial for certain physiological processes. Chemotherapy is the treatment of choice for approximately 50% of all cancers. However, multidrug resistance mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the effective...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2005.06.001

    authors: Ambudkar SV,Sauna ZE,Gottesman MM,Szakacs G

    更新日期:2005-08-01 00:00:00

  • Methylphenidate and cocaine: the same effects on gene regulation?

    abstract::Methylphenidate (Ritalin), a psychostimulant used in the treatment of Attention-Deficit Hyperactivity Disorder, has pharmacological effects similar to cocaine and amphetamine. Clinical use of methylphenidate, as well as diversion and abuse, have significantly increased during the past 10-15 years, heightening concerns...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2007.10.004

    authors: Yano M,Steiner H

    更新日期:2007-11-01 00:00:00

  • Do cannabinoids have a therapeutic role in transplantation?

    abstract::Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties. Significant clinical and experimental data on the use of cannabinoids as anti-inflammatory agents exist in many autoimmune disease settings, but virtually no studie...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2010.05.006

    authors: Nagarkatti M,Rieder SA,Hegde VL,Kanada S,Nagarkatti P

    更新日期:2010-08-01 00:00:00

  • Unveiling the role of network and systems biology in drug discovery.

    abstract::Network and systems biology offer a novel way of approaching drug discovery by developing models that consider the global physiological environment of protein targets, and the effects of modifying them, without losing the key molecular details. Here we review some recent advances in network and systems biology applied...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2009.11.006

    authors: Pujol A,Mosca R,Farrés J,Aloy P

    更新日期:2010-03-01 00:00:00

  • Targeting SREBPs for treatment of the metabolic syndrome.

    abstract::Over the past few decades, mortality resulting from cardiovascular disease (CVD) steadily decreased in western countries; however, in recent years, the decline has become offset by the increase in obesity. Obesity is strongly associated with the metabolic syndrome and its atherogenic dyslipidemia resulting from insuli...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2015.04.010

    authors: Soyal SM,Nofziger C,Dossena S,Paulmichl M,Patsch W

    更新日期:2015-06-01 00:00:00

  • NAADP: an atypical Ca2+-release messenger?

    abstract::Recently, nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown, using different techniques, to mobilize intracellular Ca2+ stores in invertebrate, lower vertebrate, plant and mammalian cells. This endogenous molecule might play an atypical role in Ca2+ signalling by coordinating the responses of other ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)01990-8

    authors: Genazzani AA,Billington RA

    更新日期:2002-04-01 00:00:00

  • Chemokines, chemokine receptors and small-molecule antagonists: recent developments.

    abstract::The physiological roles of chemokine receptors have expanded beyond host defense and now represent important targets for intervention in several disease indications. Chemokine receptors have joined the ranks of other members of the G-protein-coupled receptor (GPCR) family in therapeutic potential as small-molecule che...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(02)02064-3

    authors: Onuffer JJ,Horuk R

    更新日期:2002-10-01 00:00:00

  • Allosteric modulation of muscarinic acetylcholine receptors.

    abstract::Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(00)89023-9

    authors: Tucek S,Proska J

    更新日期:1995-06-01 00:00:00

  • Targeting inflammation and wound healing by opioids.

    abstract::Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory p...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2013.03.006

    authors: Stein C,Küchler S

    更新日期:2013-06-01 00:00:00

  • Agonist regulation of cellular G protein levels and distribution: mechanisms and functional implications.

    abstract::Exposure of cells to agonists of receptors linked to G proteins can result in downregulation of cellular levels or redistribution of G proteins from membranes to the cytosol. Agonist-induced reductions in G protein levels have been observed for members of each of the Gs, Gi and Gq families of G proteins, are likely to...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(93)90064-Q

    authors: Milligan G

    更新日期:1993-11-01 00:00:00

  • Modalities for reducing interleukin 1 activity in disease.

    abstract::The therapeutic advantage of reducing the activity of interleukin 1 (IL-1) resides in preventing its deleterious biological effects without interfering with homeostasis. As such, methods attempting to block the production or activity of IL-1 have now entered clinical trials. For example, IL-1 induction of prostaglandi...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(93)90200-4

    authors: Dinarello CA

    更新日期:1993-05-01 00:00:00

  • Human Brain Neuropharmacology: A Platform for Translational Neuroscience.

    abstract::Central nervous system (CNS) drug development has been plagued by a failure to translate effective therapies from the lab to the clinic. There are many potential reasons for this, including poor understanding of brain pharmacokinetic (PK) and pharmacodynamic (PD) factors, preclinical study flaws, clinical trial design...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2020.09.002

    authors: Dragunow M

    更新日期:2020-11-01 00:00:00

  • Non-peptide antagonists for kinin B1 receptors: new insights into their therapeutic potential for the management of inflammation and pain.

    abstract::Kinin B1 and B2 receptors are central to the aetiology of pain and inflammation. Constitutive B2 receptors are commonly associated with the acute phase of inflammation and nociception, whereas the inducible B1 receptors are mostly linked to the chronic or persistent phase (or both). Therefore, selective, orally active...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2006.10.007

    authors: Campos MM,Leal PC,Yunes RA,Calixto JB

    更新日期:2006-12-01 00:00:00

  • The developing use of heterozygous mutant mouse models in brain monoamine transporter research.

    abstract::5-Hydroxytryptamine (5-HT), dopamine and norepinephrine are important monoamine neurotransmitters implicated in multiple brain mechanisms and regulated by high-affinity transmembrane monoamine transporters. Although knockout mice lacking 5-HT, dopamine or norepinephrine transporters are widely used to assess brain mon...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2007.01.002

    authors: Kalueff AV,Ren-Patterson RF,Murphy DL

    更新日期:2007-03-01 00:00:00

  • Non-genomic loss of PTEN function in cancer: not in my genes.

    abstract::Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice wit...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2010.12.005

    authors: Leslie NR,Foti M

    更新日期:2011-03-01 00:00:00

  • Novel Therapeutic Targets for Managing Dyslipidemia.

    abstract::Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in developed nations. Therapeutic modulation of dyslipidemia by inhibiting 3'-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is standard practice throughout the world. However, based on findings from Mendelian ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2018.06.001

    authors: Sathiyakumar V,Kapoor K,Jones SR,Banach M,Martin SS,Toth PP

    更新日期:2018-08-01 00:00:00

  • Size matters in activation/inhibition of ligand-gated ion channels.

    abstract::Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. There is now growing atomic level understanding of their gating mechanisms. Although each family is unique in the architecture of the ligand-binding pocket, the pathway for motions to propagate from l...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2012.06.005

    authors: Du J,Dong H,Zhou HX

    更新日期:2012-09-01 00:00:00

  • New advances in NMDA receptor pharmacology.

    abstract::N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia and schizophrenia. The GluN2 subunits substantially contribute to functional diver...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2011.08.003

    authors: Ogden KK,Traynelis SF

    更新日期:2011-12-01 00:00:00

  • Exploring the potential of adjunct therapy in tuberculosis.

    abstract::A critical unmet need for treatment of drug-resistant tuberculosis (TB) is to find novel therapies that are efficacious, safe, and shorten the duration of treatment. Drug discovery approaches for TB primarily target essential genes of the pathogen Mycobacterium tuberculosis (Mtb) but novel strategies such as host-dire...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2015.05.005

    authors: Rayasam GV,Balganesh TS

    更新日期:2015-08-01 00:00:00

  • NADPH oxidases: novel therapeutic targets for neurodegenerative diseases.

    abstract::Oxidative stress is a key pathologic factor in neurodegenerative diseases such as Alzheimer and Parkinson diseases (AD, PD). The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a maj...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2012.03.008

    authors: Gao HM,Zhou H,Hong JS

    更新日期:2012-06-01 00:00:00

  • Adenosine A2B receptors: a novel therapeutic target in asthma?

    abstract::Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptor have been cloned: A1, A2A, A2B and A3. Significant advancement has been made in our understanding of the molecular pharma...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(98)01179-1

    authors: Feoktistov I,Polosa R,Holgate ST,Biaggioni I

    更新日期:1998-04-01 00:00:00

  • How and why do GPCRs dimerize?

    abstract::Dimerization is fairly common in the G-protein-coupled receptor (GPCR) superfamily. First attempts to rationalize this phenomenon gave rise to an idea that two receptors in a dimer could be necessary to bind a single molecule of G protein or arrestin. Although GPCRs, G proteins and arrestins were crystallized only in ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.tips.2008.02.004

    authors: Gurevich VV,Gurevich EV

    更新日期:2008-05-01 00:00:00

  • Phospholipase A2 enzymes: regulation and inhibition.

    abstract::The phospholipase A2 enzymes are important components of the cellular machinery that responds to inflammatory stimuli and maintains cell homeostasis by membrane remodelling. Their role as the rate-limiting step in the production of pro-inflammatory lipid mediators makes these enzymes an important therapeutic target fo...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(93)90071-q

    authors: Glaser KB,Mobilio D,Chang JY,Senko N

    更新日期:1993-03-01 00:00:00

  • Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature.

    abstract::The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tach...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2003.11.005

    authors: Patacchini R,Lecci A,Holzer P,Maggi CA

    更新日期:2004-01-01 00:00:00

  • Therapeutic potential of histamine H3 receptor agonists and antagonists.

    abstract::The histamine H3 receptor was discovered 15 years ago, and many potent and selective H3 receptor agonists and antagonists have since been developed. Currently, much attention is being focused on the therapeutic potential of H3 receptor ligands. In this review, Rob Leurs, Patrizio Blandina, Clark Tedford and Henk Timme...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/s0165-6147(98)01201-2

    authors: Leurs R,Blandina P,Tedford C,Timmerman H

    更新日期:1998-05-01 00:00:00

  • Cooperativity Has Empirical and Ultimate Levels of Explanation.

    abstract::Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figur...

    journal_title:Trends in pharmacological sciences

    pub_type: 评论,信件

    doi:10.1016/j.tips.2016.06.001

    authors: Ehlert FJ

    更新日期:2016-08-01 00:00:00

  • Discoidin Domains as Emerging Therapeutic Targets.

    abstract::Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2016.06.003

    authors: Villoutreix BO,Miteva MA

    更新日期:2016-08-01 00:00:00

  • Axons Matter: The Promise of Treating Neurodegenerative Disorders by Targeting SARM1-Mediated Axonal Degeneration.

    abstract::Attempts to develop neuroprotective treatments for neurodegenerative disorders have not yet been clinically successful. Axonal degeneration has been recognized as a predominant driver of disability and disease progression in central nervous system (CNS) diseases such as amyotrophic lateral sclerosis (ALS), multiple sc...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.tips.2020.01.006

    authors: Krauss R,Bosanac T,Devraj R,Engber T,Hughes RO

    更新日期:2020-04-01 00:00:00

  • Distribution and anchoring of molecular forms of acetylcholinesterase.

    abstract::Molecular forms of acetylcholinesterase exhibit tissue-specific distribution, and each form is anchored to the cell surface via a particular post-translational modification of the catalytic subunit. Nibaldo Inestrosa and Alejandra Perelman review evidence that heparan sulphate proteoglycans are the extracellular matri...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1016/0165-6147(89)90067-9

    authors: Inestrosa NC,Perelman A

    更新日期:1989-08-01 00:00:00