Molecular targets for disrupting leukocyte trafficking during multiple sclerosis.

Abstract:

:Autoimmune diseases of the central nervous system (CNS) involve the migration of abnormal numbers of self-directed leukocytes across the blood-brain barrier that normally separates the CNS from the immune system. The cardinal lesion associated with neuroinflammatory diseases is the perivascular infiltrate, which comprises leukocytes that have traversed the endothelium and have congregated in a subendothelial space between the endothelial-cell basement membrane and the glial limitans. The exit of mononuclear cells from this space can be beneficial, as when virus-specific lymphocytes enter the CNS for pathogen clearance, or might induce CNS damage, such as in the autoimmune disease multiple sclerosis when myelin-specific lymphocytes invade and induce demyelinating lesions. The molecular mechanisms involved in the movement of lymphocytes through these compartments involve multiple signalling pathways between these cells and the microvasculature. In this review, we discuss adhesion, costimulatory, cytokine, chemokine and signalling molecules involved in the dialogue between lymphocytes and endothelial cells that leads to inflammatory infiltrates within the CNS, and the targeting of these molecules as therapies for the treatment of multiple sclerosis.

journal_name

Expert Rev Mol Med

authors

McCandless EE,Klein RS

doi

10.1017/S1462399407000397

subject

Has Abstract

pub_date

2007-07-19 00:00:00

pages

1-19

issue

20

issn

1462-3994

pii

S1462399407000397

journal_volume

9

pub_type

杂志文章,评审
  • Metalloproteinases and their inhibitors in angiogenesis.

    abstract::Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is an integral part of physiological processes such as embryonic development, the female reproductive cycle and wound healing. Angiogenesis is also central to a variety of pathologies including cancer, where it is recognised as being c...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399403006628

    authors: Lafleur MA,Handsley MM,Edwards DR

    更新日期:2003-09-22 00:00:00

  • Genetic basis of human left-right asymmetry disorders.

    abstract::Humans and other vertebrates exhibit left-right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, including situs inversus and heterotaxy. Situs inversus is complete mirror-imaged arrangement of the internal organs along LR axis, wh...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2014.22

    authors: Deng H,Xia H,Deng S

    更新日期:2015-01-27 00:00:00

  • Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology.

    abstract::Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that arises from lack of expression of paternally inherited genes known to be imprinted and located in the chromosome 15q11-q13 region. PWS is considered the most common syndromal cause of life-threatening obesity and is estimated at 1 in 10,000 to 20,000 in...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399405009531

    authors: Bittel DC,Butler MG

    更新日期:2005-07-25 00:00:00

  • The heterogeneity of epithelial ovarian cancers: reconciling old and new paradigms.

    abstract::Epithelial ovarian cancer comprises several subtypes of tumours that exhibit diverse histopathological features. The intriguing assumption by many epithelial ovarian cancers of specialised features of nonovarian tissue lineages has promoted considerable debate as to whether these tumours arise from the deceptively sim...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399407000324

    authors: Naora H

    更新日期:2007-05-04 00:00:00

  • Use of mouse models in studying type 2 diabetes mellitus.

    abstract::The use of mouse models in medical research has greatly contributed to our understanding of the development of type 2 diabetes mellitus and the mechanisms of disease progression in the context of insulin resistance and β-cell dysfunction. Maintenance of glucose homeostasis involves a complex interplay of many genes an...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399410001729

    authors: Lee AW,Cox RD

    更新日期:2011-01-06 00:00:00

  • Molecular mechanisms underlying nutrient-stimulated incretin secretion.

    abstract::The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells in the intestinal epithelium in response to nutrient ingestion. The actions of GLP-1 and GIP - not only on local gut physiology but also on glucose homeostasis, appetite ...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S146239940900132X

    authors: Parker HE,Reimann F,Gribble FM

    更新日期:2010-01-05 00:00:00

  • Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury.

    abstract::Spinal cord injury is one of the most devastating conditions that affects the central nervous system. It can lead to permanent disability and there are around two million people affected worldwide. After injury, accumulation of myelin debris and formation of an inhibitory glial scar at the site of injury leads to a ph...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章

    doi:10.1017/S1462399409001288

    authors: Afshari FT,Kappagantula S,Fawcett JW

    更新日期:2009-12-08 00:00:00

  • Connexin-26 mutations in deafness and skin disease.

    abstract::Gap junctions allow the exchange of ions and small molecules between adjacent cells through intercellular channels formed by connexin proteins, which can also form functional hemichannels in nonjunctional membranes. Mutations in connexin genes cause a variety of human diseases. For example, mutations in GJB2, the gene...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399409001276

    authors: Lee JR,White TW

    更新日期:2009-11-19 00:00:00

  • Mitochondrial quality control and neurological disease: an emerging connection.

    abstract::The human brain is a highly complex organ with remarkable energy demands. Although it represents only 2% of the total body weight, it accounts for 20% of all oxygen consumption, reflecting its high rate of metabolic activity. Mitochondria have a crucial role in the supply of energy to the brain. Consequently, their de...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399410001456

    authors: de Castro IP,Martins LM,Tufi R

    更新日期:2010-04-19 00:00:00

  • The phosphoinositide 3-kinase pathway and cancer.

    abstract::Human tumours emerge as the result of multiple genetic and epigenetic aberrations that allow the proto-cancer cell to escape normal social control. Many signal transduction pathways become constitutively active during this process, and one whose importance is increasingly being appreciated involves phosphoinositide 3-...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399405009361

    authors: Stokoe D

    更新日期:2005-06-06 00:00:00

  • Adipose-derived stromal cells for osteoarticular repair: trophic function versus stem cell activity.

    abstract::The identification of multipotent adipose-derived stromal cells (ASC) has raised hope that tissue regeneration approaches established with bone-marrow-derived stromal cells (BMSC) can be reproduced with a cell-type that is far more accessible in large quantities. Recent detailed comparisons, however, revealed subtle f...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2014.9

    authors: Ruetze M,Richter W

    更新日期:2014-05-09 00:00:00

  • Ex-vivo ocular surface stem cell therapies: current techniques, applications, hurdles and future directions.

    abstract::Engineered tissue derived from ocular surface stem cells (SCs) are a cutting edge biotechnology for repair and restoration of severely damaged eyes as a result of ocular surface dysfunction because of SC failure. Ex-vivo SC expansion techniques have advanced significantly since the first patients were treated in the l...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2013.5

    authors: Angunawela RI,Mehta JS,Daniels JT

    更新日期:2013-06-25 00:00:00

  • Atherosclerosis: role of chemokines and macrophages.

    abstract::Atherosclerosis is a pathological process that takes place in the major arteries and is the underlying cause of heart attacks, stroke and peripheral artery disease. The earliest detectable lesions, called fatty streaks, contain macrophage foam cells that are derived from recruited monocytes. More-advanced atherosclero...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章

    doi:10.1017/S1462399401003696

    authors: Lucas AD,Greaves DR

    更新日期:2001-11-05 00:00:00

  • Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas.

    abstract::The mammalian target of rapamycin mTOR is a central element in an evolutionary conserved signalling pathway that regulates cell growth, survival and proliferation, orchestrating signals originating from growth factors, nutrients or particular stress stimuli. Two important modulators of mTOR activity are the AKT and ER...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399408000586

    authors: Drakos E,Rassidakis GZ,Medeiros LJ

    更新日期:2008-02-04 00:00:00

  • The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology.

    abstract::Common to all forms of chronic kidney disease is the progressive scarring of the tubulo-interstitial space, associated with the acquisition and accumulation of activated myofibroblasts. Many of these myofibroblasts are generated when tubular epithelial cells progressively lose their epithelial characteristics (cell-ce...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399410001481

    authors: Burns WC,Thomas MC

    更新日期:2010-05-27 00:00:00

  • New targeted therapies for treatment of thrombosis in antiphospholipid syndrome.

    abstract::Antiphospholipid (aPL) antibodies (Abs) are associated with thrombosis and pregnancy loss in antiphospholipid syndrome (APS), a disorder initially characterised in patients with systemic lupus erythematosus (SLE) but now known to occur in the absence of other autoimmune disease. There is strong evidence that aPL Abs a...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399407000506

    authors: Pierangeli SS,Vega-Ostertag ME,González EB

    更新日期:2007-11-13 00:00:00

  • Molecular mechanisms of learning and memory.

    abstract::Memory is the process by which organisms are able to record their experiences, and use this information to adapt their responses to the environment. As such, it is vital for survival. In recent years, the development of spatially and temporally selective techniques for the regulation of gene expression has allowed the...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399403006707

    authors: Dunning J,During MJ

    更新日期:2003-10-07 00:00:00

  • Cooperative integration between HEDGEHOG-GLI signalling and other oncogenic pathways: implications for cancer therapy.

    abstract::The HEDGEHOG-GLI (HH-GLI) signalling is a key pathway critical in embryonic development, stem cell biology and tissue homeostasis. In recent years, aberrant activation of HH-GLI signalling has been linked to several types of cancer, including those of the skin, brain, lungs, prostate, gastrointestinal tract and blood....

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2015.3

    authors: Pandolfi S,Stecca B

    更新日期:2015-02-09 00:00:00

  • Costamere proteins and their involvement in myopathic processes.

    abstract::Muscle fibres are very specialised cells with a complex structure that requires a high level of organisation of the constituent proteins. For muscle contraction to function properly, there is a need for not only sarcomeres, the contractile structures of the muscle fibre, but also costameres. These are supramolecular s...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2015.9

    authors: Jaka O,Casas-Fraile L,López de Munain A,Sáenz A

    更新日期:2015-06-19 00:00:00

  • SOCS proteins in T helper cell differentiation: implications for allergic disorders?

    abstract::Asthma, allergic rhinitis and atopic dermatitis are allergic immune disorders characterised by a predominance of T helper 2 (Th2) cells, the resulting elevation of allergen-specific IgE, and mast-cell- and basophil-associated inflammation. The cytokine environment at the site of the initial antigen stimulation determi...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399404008348

    authors: Inoue H,Kubo M

    更新日期:2004-10-22 00:00:00

  • The interaction of macrophage receptors with bacterial ligands.

    abstract::Innate immune receptors play a key role in the early recognition of invading bacterial pathogens and initiate the crucial innate immune response. The diverse macrophage receptors recognise Gram-positive and Gram-negative bacteria via conserved structures on the bacterial surface and facilitate phagocytosis and/or sign...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399406000159

    authors: Plüddemann A,Mukhopadhyay S,Gordon S

    更新日期:2006-11-22 00:00:00

  • Advances in the molecular genetics of non-syndromic polydactyly.

    abstract::Polydactyly is one of the most common inherited limb abnormalities, characterised by supernumerary fingers or toes. It results from disturbances in the normal programme of the anterior-posterior axis of the developing limb, with diverse aetiology and variable inter- and intra-familial clinical features. Polydactyly ca...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2015.18

    authors: Deng H,Tan T,Yuan L

    更新日期:2015-10-30 00:00:00

  • Mechanisms of disease: the endocrinology of ectopic pregnancy.

    abstract::Ectopic pregnancy is defined as a pregnancy implanted outside the uterus, and >98% implant in the Fallopian tube. It has a major clinical and socioeconomic impact worldwide. The diagnosis of ectopic pregnancy is often difficult and resource intensive owing to a lack of accurate biomarkers, and there is a need for impr...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2011.2

    authors: Horne AW,Critchley HO

    更新日期:2012-03-02 00:00:00

  • Hypothalamic orexins/hypocretins as regulators of breathing.

    abstract::It was suggested half a century ago that electrical impulses from the lateral hypothalamic area stimulate breathing. It is now emerging that these effects may be mediated, at least in part, by neurons containing orexin neuropeptides (also known as hypocretins). These cells promote wakefulness and consciousness, and th...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399408000823

    authors: Williams RH,Burdakov D

    更新日期:2008-10-02 00:00:00

  • Strategies for cancer therapy using carcinoembryonic antigen vaccines.

    abstract::Advances in molecular biology and immunology have renewed interest in the development of vaccines for the treatment or prevention of cancer. Research over the past 10 years has focused on the identification of suitable tumour antigens to use as targets for a variety of vaccine strategies. Carcinoembryonic antigen (CEA...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章

    doi:10.1017/S146239940000168X

    authors: Hörig H,Medina FA,Conkright WA,Kaufman HL

    更新日期:2000-04-19 00:00:00

  • Angiopoietin-like-2: a multifaceted protein with physiological and pathophysiological properties.

    abstract::Angptl2 is a multifaceted protein, displaying both physiological and pathological functions, in which scientific and clinical interest is growing exponentially within the past few years. Its physiological functions are not well understood, but angptl2 was first acknowledged for its pro-angiogenic and antiapoptotic cap...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/erm.2014.19

    authors: Thorin-Trescases N,Thorin E

    更新日期:2014-11-24 00:00:00

  • Molecular mechanisms controlling human adipose tissue development: insights from monogenic lipodystrophies.

    abstract::Appropriately functioning adipose tissue is essential for human health, a fact most clearly illustrated by individuals with lipodystrophy, who have impaired adipose development and often suffer severe metabolic disease as a result. Humans with obesity display a similar array of metabolic problems. This reflects failur...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399410001547

    authors: Rochford JJ

    更新日期:2010-08-02 00:00:00

  • Molecular mechanisms of endothelial hyperpermeability: implications in inflammation.

    abstract::Endothelial hyperpermeability is a significant problem in vascular inflammation associated with trauma, ischaemia-reperfusion injury, sepsis, adult respiratory distress syndrome, diabetes, thrombosis and cancer. An important mechanism underlying this process is increased paracellular leakage of plasma fluid and protei...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399409001112

    authors: Kumar P,Shen Q,Pivetti CD,Lee ES,Wu MH,Yuan SY

    更新日期:2009-06-30 00:00:00

  • Cellular and molecular mechanisms that underlie Entamoeba histolytica pathogenesis: prospects for intervention.

    abstract::The protozoan parasite Entamoeba histolytica is the causative agent of amoebic dysentery. It is prevalent in developing countries that cannot prevent its fecal-oral spread and ranks second in worldwide causes of morbidity by parasitic infection. Improvements in sanitation would help curb disease spread. However, a lac...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399405009622

    authors: Laughlin RC,Temesvari LA

    更新日期:2005-07-18 00:00:00

  • Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions.

    abstract::Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicized isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), ...

    journal_title:Expert reviews in molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1017/S1462399404008300

    authors: Geisbert TW,Hensley LE

    更新日期:2004-09-21 00:00:00