Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke.

Abstract:

:Stroke is a major cause of serious disability due to the brain's limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular and neuronal repair, resulting in permanent functional deficits. Although clinical evidence indicates that revascularization of the ischemic brain regions is crucial for functional recovery, no therapeutics that promote angiogenesis after cerebral stroke are currently available. Besides vascular growth factors, guidance molecules have been identified to regulate aspects of angiogenesis in the central nervous system (CNS) and may provide targets for therapeutic angiogenesis. In this study, we demonstrate that genetic deletion of the neurite outgrowth inhibitor Nogo-A or one of its corresponding receptors, S1PR2, improves vascular sprouting and repair and reduces neurological deficits after cerebral ischemia in mice. These findings were reproduced in a therapeutic approach using intrathecal anti-Nogo-A antibodies; such a therapy is currently in clinical testing for spinal cord injury. These results provide a basis for a therapeutic blockage of inhibitory guidance molecules to improve vascular and neural repair after ischemic CNS injuries.

authors

Rust R,Grönnert L,Gantner C,Enzler A,Mulders G,Weber RZ,Siewert A,Limasale YDP,Meinhardt A,Maurer MA,Sartori AM,Hofer AS,Werner C,Schwab ME

doi

10.1073/pnas.1905309116

subject

Has Abstract

pub_date

2019-07-09 00:00:00

pages

14270-14279

issue

28

eissn

0027-8424

issn

1091-6490

pii

1905309116

journal_volume

116

pub_type

杂志文章
  • A high-resolution landscape of mutations in the BCL6 super-enhancer in normal human B cells.

    abstract::The super-enhancers (SEs) of lineage-specific genes in B cells are off-target sites of somatic hypermutation. However, the inability to detect sufficient numbers of mutations in normal human B cells has precluded the generation of a high-resolution mutational landscape of SEs. Here we captured and sequenced 12 B cell ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1914163116

    authors: Shen JC,Kamath-Loeb AS,Kohrn BF,Loeb KR,Preston BD,Loeb LA

    更新日期:2019-12-03 00:00:00

  • Evidence for the involvement of sulfhydryl oxidation in the regulation of fat cell hexose transport by insulin.

    abstract::Previous studies have shown that the oxidants Cu(++), H(2)O(2), and diamide mimic the stimulatory effect of insulin on 3-O-methylglucose transport in isolated fat cells. The present experiments were designed to determine whether sulfhydryl oxidation plays a key role in the activation of the glucose transport system. I...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.10.4173

    authors: Czech MP,Lawrence JC Jr,Lynn WS

    更新日期:1974-10-01 00:00:00

  • Raman resonance of electron donor/acceptor complex.

    abstract::The resonance Raman excitation profiles of a number of charge transfer transitions in electron donor/acceptor complexes with tetracyanoethylene as acceptor in solution at room temperature are reported and compared with absorption and fluorescence spectra of these complexes. All complexes show distinct anomalies which ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.11.4196

    authors: Michaelian KH,Rieckhoff KE,Voigt EM

    更新日期:1975-11-01 00:00:00

  • Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells.

    abstract::The polyamines, putrescine, spermidine, and spermine, are essential polycations, intimately involved in the regulation of cellular proliferation. Although polyamines exert dynamic effects on the conformation of nucleic acids and macromolecular synthesis in vitro, their specific functions in vivo are poorly understood....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1219002110

    authors: Mandal S,Mandal A,Johansson HE,Orjalo AV,Park MH

    更新日期:2013-02-05 00:00:00

  • Limits of multifunctionality in tunable networks.

    abstract::Nature is rife with networks that are functionally optimized to propagate inputs to perform specific tasks. Whether via genetic evolution or dynamic adaptation, many networks create functionality by locally tuning interactions between nodes. Here we explore this behavior in two contexts: strain propagation in mechanic...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1806790116

    authors: Rocks JW,Ronellenfitsch H,Liu AJ,Nagel SR,Katifori E

    更新日期:2019-02-12 00:00:00

  • Functional organization of the cat's visual cortex after prenatal interruption of binocular interactions.

    abstract::The functional consequences of interrupting in utero binocular interactions were studied by recording from single cells in area 17 of adult cats that had one eye removed at least 2 wk before birth. In these animals all cortical neurons could be driven by the remaining eye, and in tangential microelectrode penetrations...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.11.3901

    authors: Shook BL,Maffei L,Chalupa LM

    更新日期:1985-06-01 00:00:00

  • Dpb11, which interacts with DNA polymerase II(epsilon) in Saccharomyces cerevisiae, has a dual role in S-phase progression and at a cell cycle checkpoint.

    abstract::DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid. The nucleotide sequence of the DPB11 gene revealed an open reading frame predicting an 87-kDa protein. This protein is homologous to th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.25.11791

    authors: Araki H,Leem SH,Phongdara A,Sugino A

    更新日期:1995-12-05 00:00:00

  • Evidence that tumor antigens enhance tumor growth in vivo by interacting with a radiosensitive (suppressor?) cell population.

    abstract::The growth of a small number of cells from each of two chemically induced BALB/c sarcomas was enhanced when x-irradiated (15,000 rads) cells of the same sarcoma were mixed with the tumor inoculum. This enhancement did not occur if the recipients had been given a total body x-irradiation of 450 rads. Tumor neutralizati...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.1.436

    authors: Hellström KE,Hellström I

    更新日期:1978-01-01 00:00:00

  • The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice.

    abstract::The A(2A)R is largely coexpressed with D(2)Rs and enkephalin mRNA in the striatum where it modulates dopaminergic activity. Activation of the A(2A)R antagonizes D(2)R-mediated behavioral and neurochemical effects in the basal ganglia through a mechanism that may involve direct A(2A)R-D(2)R interaction. However, whethe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.98.4.1970

    authors: Chen JF,Moratalla R,Impagnatiello F,Grandy DK,Cuellar B,Rubinstein M,Beilstein MA,Hackett E,Fink JS,Low MJ,Ongini E,Schwarzschild MA

    更新日期:2001-02-13 00:00:00

  • Telomere shortening is a hallmark of genetic cardiomyopathies.

    abstract::This study demonstrates that significantly shortened telomeres are a hallmark of cardiomyocytes (CMs) from individuals with end-stage hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) as a result of heritable defects in cardiac proteins critical to contractile function. Positioned at the ends of chromo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1714538115

    authors: Chang ACY,Chang ACH,Kirillova A,Sasagawa K,Su W,Weber G,Lin J,Termglinchan V,Karakikes I,Seeger T,Dainis AM,Hinson JT,Seidman J,Seidman CE,Day JW,Ashley E,Wu JC,Blau HM

    更新日期:2018-09-11 00:00:00

  • The dynamic phagosomal proteome and the contribution of the endoplasmic reticulum.

    abstract::Macrophages use phagocytosis to control the spread of pathogens in the body, to clear apoptotic cells, and to aid in tissue remodeling. The phagosomal membrane is traditionally thought to originate from the plasmalemma and then go through a series of maturation steps involving sequential fusion with endosomal compartm...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0705801104

    authors: Rogers LD,Foster LJ

    更新日期:2007-11-20 00:00:00

  • Human leukemia-associated anti-nuclear reactivity.

    abstract::A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.3.685

    authors: Klein G,Steiner M,Wiener F,Klein E

    更新日期:1974-03-01 00:00:00

  • Human response against NP-4, a mouse antibody to carcinoembryonic antigen: human anti-idiotype antibodies mimic an epitope on the tumor antigen.

    abstract::Anti-idiotype antibodies (Ab2) were purified from a cancer patient treated with NP-4, a murine monoclonal antibody to carcinoembryonic antigen (CEA). These Ab2 were specific for NP-4 and inhibited the binding between NP-4 and CEA. BALB/c mice immunized with these human Ab2 produced anti-Ab2 antibodies that were also r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.8.3421

    authors: Losman MJ,Hansen HJ,Sharkey RM,Goldenberg DM,Monestier M

    更新日期:1991-04-15 00:00:00

  • Interdomain movements in metabotropic glutamate receptor activation.

    abstract::Many cell surface receptors are multimeric proteins, composed of several structural domains, some involved in ligand recognition, whereas others are responsible for signal transduction. In most cases, the mechanism of how ligand interaction in the extracellular domains leads to the activation of effector domains remai...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1107775108

    authors: Huang S,Cao J,Jiang M,Labesse G,Liu J,Pin JP,Rondard P

    更新日期:2011-09-13 00:00:00

  • Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning.

    abstract::Higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (PFC). Alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. Prefrontal serotonin (5-HT)2A receptors play an essential role in cortical net...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1525586113

    authors: Barre A,Berthoux C,De Bundel D,Valjent E,Bockaert J,Marin P,Bécamel C

    更新日期:2016-03-08 00:00:00

  • Differences in alpha and beta polypeptide chains of tubulin resolved by electron microscopy with image reconstruction.

    abstract::Electron microscopic techniques have been used to reveal two classes of subunits of tubulin in ordered arrays. Presumably the two classes correspond to the alpha and beta polypeptide chains of tubulin that have been distinguished by chemical criteria. The two types of subunits alternate along individual protofilaments...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.10.5006

    authors: Crepeau RH,McEwen B,Edelstein SJ

    更新日期:1978-10-01 00:00:00

  • Growing up blind does not change the neural bases of Theory of Mind.

    abstract::Humans reason about the mental states of others; this capacity is called Theory of Mind (ToM). In typically developing adults, ToM is supported by a consistent group of brain regions: the bilateral temporoparietal junction (TPJ), medial prefrontal cortex (MPFC), precuneus (PC), and anterior temporal sulci (aSTS). How ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0900010106

    authors: Bedny M,Pascual-Leone A,Saxe RR

    更新日期:2009-07-07 00:00:00

  • Estrogen differentially regulates neuropeptide gene expression in a sexually dimorphic olfactory pathway.

    abstract::The posterodorsal part of the medial nucleus of the amygdala (MeAp) receives its major sensory input from the accessory olfactory bulb and projects massively to the medial preoptic nucleus and other sexually dimorphic hypothalamic nuclei thought to play key roles in mediating steroid-sensitive reproductive functions. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.12.4766

    authors: Simerly RB,Young BJ,Capozza MA,Swanson LW

    更新日期:1989-06-01 00:00:00

  • Lessons learned and concepts formed from study of the pathogenesis of the two negative-strand viruses lymphocytic choriomeningitis and influenza.

    abstract::Viruses have unique lifestyles. To describe the pathogenesis and significance of viral infection in terms of host responses, resultant injury, and therapy, we focused on two RNA viruses: lymphocytic choriomeningitis (LCMV) and influenza (Flu). Many of the currently established concepts and consequences about viruses a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.1222025110

    authors: Oldstone MB

    更新日期:2013-03-12 00:00:00

  • Separation of positional isomers of oligosaccharides and glycopeptides by high-performance anion-exchange chromatography with pulsed amperometric detection.

    abstract::High-performance anion-exchange (HPAE) chromatography under alkaline conditions (pH congruent to 13) has been found to efficiently separate neutral oligosaccharides (triose to undecaose) according to molecular size, sugar composition, and linkage of monosaccharide units. The method was able to resolve 1----3, 1----4, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.10.3289

    authors: Hardy MR,Townsend RR

    更新日期:1988-05-01 00:00:00

  • Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice.

    abstract::The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.5.1299

    authors: Andres AC,Schönenberger CA,Groner B,Hennighausen L,LeMeur M,Gerlinger P

    更新日期:1987-03-01 00:00:00

  • Kinetics of p56lck and p60src Src homology 2 domain binding to tyrosine-phosphorylated peptides determined by a competition assay or surface plasmon resonance.

    abstract::Src homology 2 (SH2) domains are phosphotyrosine-binding modules found within various signal-transducing proteins. We have determined by 125I competition assay and surface plasmon resonance that the SH2 domains of Src and Lck bind to a variety of phosphopeptides with similar affinity and specificity. Both bound with h...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.11.4902

    authors: Payne G,Shoelson SE,Gish GD,Pawson T,Walsh CT

    更新日期:1993-06-01 00:00:00

  • Oligonucleotide-directed site-specific mutagenesis in Drosophila melanogaster.

    abstract::An efficient technique has been developed for performing in vivo site-directed mutagenesis in Drosophila melanogaster. This procedure involves directed repair of P-element-induced DNA lesions after injection of a modified DNA sequence into early embryos. An oligonucleotide of 50 base pairs, whose sequence spans the P-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.5.1735

    authors: Banga SS,Boyd JB

    更新日期:1992-03-01 00:00:00

  • D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release.

    abstract::Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D-ser...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.9.3948

    authors: Schell MJ,Molliver ME,Snyder SH

    更新日期:1995-04-25 00:00:00

  • On the stereochemistry and biosynthesis of lipoxin B.

    abstract::Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes. Comparison with a number of trihydroxyicosatetraenes prepared by total synthesis showed that biologically derived LXB is (5S,14R,15S)-5,14,15-trihydroxy-6,10,12-trans-8-cis-icos...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.7.1983

    authors: Serhan CN,Hamberg M,Samuelsson B,Morris J,Wishka DG

    更新日期:1986-04-01 00:00:00

  • Oil platforms off California are among the most productive marine fish habitats globally.

    abstract::Secondary (i.e., heterotrophic or animal) production is a main pathway of energy flow through an ecosystem as it makes energy available to consumers, including humans. Its estimation can play a valuable role in the examination of linkages between ecosystem functions and services. We found that oil and gas platforms of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1411477111

    authors: Claisse JT,Pondella DJ 2nd,Love M,Zahn LA,Williams CM,Williams JP,Bull AS

    更新日期:2014-10-28 00:00:00

  • Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells.

    abstract::Vascular endothelial cells (ECs) sense and respond to hemodynamic shear stress, which is critical for circulatory homeostasis and the pathophysiology of vascular diseases. The mechanisms of shear stress mechanotransduction, however, remain elusive. We previously demonstrated a direct role of mitochondria in the purine...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2014029117

    authors: Yamamoto K,Nogimori Y,Imamura H,Ando J

    更新日期:2020-12-29 00:00:00

  • Multiple gamma-crystallins of the mouse lens: fractionation of mRNAs by cDNA cloning.

    abstract::cDNAs made from polyadenylylated RNAs of the mouse lens were cloned by the G.C tailing procedure in the bacterial plasmid pBR322. Four recombinant DNAs containing gamma-crystallin sequences were identified by hybrid selection and translation. Sequence analysis of the in vivo-labeled gamma-crystallin polypeptides that ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.9.2783

    authors: Shinohara T,Robinson EA,Appella E,Piatigorsky J

    更新日期:1982-05-01 00:00:00

  • Endonuclease III (nth) mutants of Escherichia coli.

    abstract::Two strains that overproduce endonuclease III were found in a colony bank containing hybrid ColE1-Escherichia coli plasmids. The enzyme was identified in crude extracts by the degradation of partially depyrimidinated DNA in the presence of EDTA, by its sedimentation velocity, and by its associated thymine glycol-DNA g...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.2.474

    authors: Cunningham RP,Weiss B

    更新日期:1985-01-01 00:00:00

  • Superfamily Gondwanatherioidea: a previously unrecognized radiation of multituberculate mammals in South America.

    abstract::Multituberculates were the longest-lived order of the Class Mammalia and, during the Mesozoic and early Cenozoic, were among the most diverse and abundant representatives of the class. However, until the recent discovery of two Cretaceous teeth, one from South America and one from Africa, they were known only from nor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.90.20.9379

    authors: Krause DW,Bonaparte JF

    更新日期:1993-10-15 00:00:00