A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone.

Abstract:

:Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signaling. 7,8-Dihydroxyflavone protected wild-type, but not TrkB-deficient, neurons from apoptosis. Administration of 7,8-dihydroxyflavone to mice activated TrkB in the brain, inhibited kainic acid-induced toxicity, decreased infarct volumes in stroke in a TrkB-dependent manner, and was neuroprotective in an animal model of Parkinson disease. Thus, 7,8-dihydroxyflavone imitates BDNF and acts as a robust TrkB agonist, providing a powerful therapeutic tool for the treatment of various neurological diseases.

authors

Jang SW,Liu X,Yepes M,Shepherd KR,Miller GW,Liu Y,Wilson WD,Xiao G,Blanchi B,Sun YE,Ye K

doi

10.1073/pnas.0913572107

subject

Has Abstract

pub_date

2010-02-09 00:00:00

pages

2687-92

issue

6

eissn

0027-8424

issn

1091-6490

pii

0913572107

journal_volume

107

pub_type

杂志文章
  • An invariant aspartic acid in the DNA glycosylase domain of DEMETER is necessary for transcriptional activation of the imprinted MEDEA gene.

    abstract::Helix-hairpin-helix DNA glycosylases are typically small proteins that initiate repair of DNA by excising damaged or mispaired bases. An invariant aspartic acid in the active site is involved in catalyzing the excision reaction. Replacement of this critical residue with an asparagine severely reduces catalytic activit...

    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.0402328101

    authors: Choi Y,Harada JJ,Goldberg RB,Fischer RL

    更新日期:2004-05-11 00:00:00

  • The role of nanostructure in the wetting behavior of mixed-monolayer-protected metal nanoparticles.

    abstract::Self-assembled monolayer-protected nanoparticles are promising candidates for applications, such as sensing and drug delivery, in which the molecular ligands' interactions with the surrounding environment play a crucial role. We recently showed that, when gold nanoparticles are coated with a binary mixture of immiscib...

    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.0803929105

    authors: Centrone A,Penzo E,Sharma M,Myerson JW,Jackson AM,Marzari N,Stellacci F

    更新日期:2008-07-22 00:00:00

  • Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes.

    abstract::We provide here evidence that supports the occurrence of a biologically dormant form of selectin ligand carbohydrate, the sialyl 6-sulfo Lewis X containing modified sialic acid, in human leukocytes. The modification of sialic acid involves first de-N-acetylation of sialic acid moiety through ubiquitous de-N-acetylatio...

    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.96.4.1597

    authors: Mitsuoka C,Ohmori K,Kimura N,Kanamori A,Komba S,Ishida H,Kiso M,Kannagi R

    更新日期:1999-02-16 00:00:00

  • A theoretical examination of the factors controlling the catalytic efficiency of the DNA-(adenine-N6)-methyltransferase from Thermus aquaticus.

    abstract::Ab initio and density functional calculations have been carried out to more fully understand the factors controlling the catalytic activity of the Thermus aquaticus DNA methyltransferase (MTaqI) in the N-methylation at the N(6) of an adenine nucleobase. The noncatalyzed reaction was modeled as a methyl transfer from t...

    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.122231499

    authors: Newby ZE,Lau EY,Bruice TC

    更新日期:2002-06-11 00:00:00

  • Mitogenic properties of a calcium ionophore, A23187.

    abstract::A23187 is a carboxylic antibiotic that selectively transfers calcium, magnesium, and other divalent cations across biologic membranes. This ionophore was found to produce morphologic blast transformation, DNA synthesis, and mitosis in human lymphocytes. Several hours of ionophore-cell contact were necessary to produce...

    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.71.12.5088

    authors: Luckasen JR,White JG,Kersey JH

    更新日期:1974-12-01 00:00:00

  • Generation of cell-to-cell signals in quorum sensing: acyl homoserine lactone synthase activity of a purified Vibrio fischeri LuxI protein.

    abstract::Many bacteria use acyl homoserine lactone signals to monitor cell density in a type of gene regulation termed quorum sensing and response. Synthesis of these signals is directed by homologs of the luxi gene of Vibrio fischeri. This communication resolves two critical issues concerning the synthesis of the V. fischeri ...

    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.93.18.9505

    authors: Schaefer AL,Val DL,Hanzelka BL,Cronan JE Jr,Greenberg EP

    更新日期:1996-09-03 00:00:00

  • Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI.

    abstract::Recent functional imaging studies have revealed coactivation in a distributed network of cortical regions that characterizes the resting state, or default mode, of the human brain. Among the brain regions implicated in this network, several, including the posterior cingulate cortex and inferior parietal lobes, have al...

    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.0308627101

    authors: Greicius MD,Srivastava G,Reiss AL,Menon V

    更新日期:2004-03-30 00:00:00

  • Allorecognition of purified major histocompatibility complex glycoproteins by cytotoxic T lymphocytes.

    abstract::To investigate how T cells recognize allogeneic class I proteins encoded by the major histocompatibility complex (MHC), we examined the human cytotoxic T lymphocytes (CTL) elicited in a mixed lymphocyte reaction against a lymphoblastoid B-cell line (JY) whose MHC-class I proteins are HLA-A2 and -B7. By panning the res...

    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.85.8.2728

    authors: Elliott TJ,Eisen HN

    更新日期:1988-04-01 00:00:00

  • Immunological defect and its correction in the osteopetrotic mutant rat.

    abstract::Congenital osteopetrosis in the mutant rat "op" is accompanied by early atrophy of the thymus gland. The response of thymocytes to concanavalin A and phytohemagglutinin P was greatly diminished at age 28 days, even before pronounced thymic atrophy could be detected. The response of spleen cells to mitogens that stimul...

    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.74.1.339

    authors: Milhaud G,Labat ML,Parant M,Damais C,Chedid L

    更新日期:1977-01-01 00:00:00

  • Highly infectious prions are not directly neurotoxic.

    abstract::Prions are infectious agents which cause rapidly lethal neurodegenerative diseases in humans and animals following long, clinically silent incubation periods. They are composed of multichain assemblies of misfolded cellular prion protein. While it has long been assumed that prions are themselves neurotoxic, recent dev...

    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.2007406117

    authors: Benilova I,Reilly M,Terry C,Wenborn A,Schmidt C,Marinho AT,Risse E,Al-Doujaily H,Wiggins De Oliveira M,Sandberg MK,Wadsworth JDF,Jat PS,Collinge J

    更新日期:2020-09-22 00:00:00

  • Evolution of insulin at the edge of foldability and its medical implications.

    abstract::Proteins have evolved to be foldable, and yet determinants of foldability may be inapparent once the native state is reached. Insight has emerged from studies of diseases of protein misfolding, exemplified by monogenic diabetes mellitus due to mutations in proinsulin leading to endoplasmic reticulum stress and β-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.2010908117

    authors: Rege NK,Liu M,Yang Y,Dhayalan B,Wickramasinghe NP,Chen YS,Rahimi L,Guo H,Haataja L,Sun J,Ismail-Beigi F,Phillips NB,Arvan P,Weiss MA

    更新日期:2020-11-24 00:00:00

  • Place recognition and heading retrieval are mediated by dissociable cognitive systems in mice.

    abstract::A lost navigator must identify its current location and recover its facing direction to restore its bearings. We tested the idea that these two tasks--place recognition and heading retrieval--might be mediated by distinct cognitive systems in mice. Previous work has shown that numerous species, including young childre...

    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.1424194112

    authors: Julian JB,Keinath AT,Muzzio IA,Epstein RA

    更新日期:2015-05-19 00:00:00

  • The murMN operon: a functional link between antibiotic resistance and antibiotic tolerance in Streptococcuspneumoniae.

    abstract::Inactivation of the recently identified murMN operon in penicillin-resistant strains of Streptococcus pneumoniae was shown already to cause two major effects: elimination of branched-structured muropeptides from the cell wall and complete loss of penicillin resistance. We now show that cells with inactivated murMN als...

    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.032671699

    authors: Filipe SR,Severina E,Tomasz A

    更新日期:2002-02-05 00:00:00

  • Curved DNA: design, synthesis, and circularization.

    abstract::Curved DNA molecules and unusually small circles have been obtained by ligation of synthetic 21-base precursors: (sequence in text). The ligation resulted in the formation of double-stranded oligo-(precursor)s possessing a strong 10.5-base-pair (bp) periodicity of the runs of adenines. Two-dimensional polyacrylamide 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.83.4.862

    authors: Ulanovsky L,Bodner M,Trifonov EN,Choder M

    更新日期:1986-02-01 00:00:00

  • Topological mapping of acetylcholine receptor: evidence for a model with five transmembrane segments and a cytoplasmic COOH-terminal peptide.

    abstract::Antibodies were raised against two synthetic peptides whose sequences correspond respectively to the COOH-terminal end (residues 501-516) of the protein encoded by the gene for the delta chain and to a proposed cytoplasmic region (residues 350-358) of the beta chain of the acetylcholine receptor from Torpedo californi...

    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.82.2.626

    authors: Young EF,Ralston E,Blake J,Ramachandran J,Hall ZW,Stroud RM

    更新日期:1985-01-01 00:00:00

  • Chimpanzee super strength and human skeletal muscle evolution.

    abstract::Since at least the 1920s, it has been reported that common chimpanzees (Pan troglodytes) differ from humans in being capable of exceptional feats of "super strength," both in the wild and in captive environments. A mix of anecdotal and more controlled studies provides some support for this view; however, a critical re...

    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.1619071114

    authors: O'Neill MC,Umberger BR,Holowka NB,Larson SG,Reiser PJ

    更新日期:2017-07-11 00:00:00

  • Spectrophotometric assay for enzyme-mediated unwinding of double-stranded DNA.

    abstract::A method is described for monitoring the enzyme-mediated unwinding of duplex DNA spectrophotometrically. The assay employs a partially duplex oligonucleotide substrate modified at the complementary end with coumarin and fluorescein moieties. When in close proximity the fluorescein quenches the fluorescence of coumarin...

    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.91.12.5471

    authors: Houston P,Kodadek T

    更新日期:1994-06-07 00:00:00

  • Experience sampling during fMRI reveals default network and executive system contributions to mind wandering.

    abstract::Although mind wandering occupies a large proportion of our waking life, its neural basis and relation to ongoing behavior remain controversial. We report an fMRI study that used experience sampling to provide an online measure of mind wandering during a concurrent task. Analyses focused on the interval of time immedia...

    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.0900234106

    authors: Christoff K,Gordon AM,Smallwood J,Smith R,Schooler JW

    更新日期:2009-05-26 00:00:00

  • Evolution of a mass spectrometry-grade protease with PTM-directed specificity.

    abstract::Mapping posttranslational modifications (PTMs), which diversely modulate biological functions, represents a significant analytical challenge. The centerpiece technology for PTM site identification, mass spectrometry (MS), requires proteolytic cleavage in the vicinity of a PTM to yield peptides for sequencing. This req...

    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.1609925113

    authors: Tran DT,Cavett VJ,Dang VQ,Torres HL,Paegel BM

    更新日期:2016-12-20 00:00:00

  • Inhibition of the activation of Hageman factor (factor XII) by human vascular endothelial cell culture supernates.

    abstract::The supernatant fluid (conditioned medium) of cultured human vascular endothelial cells inhibits activation of Hageman factor (factor XII), whether by ellagic acid, bovine brain sulfatides, or bismuth subgallate; inhibition appears to be a property of one or more proteins in the culture supernates. This phenomenon may...

    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.88.23.10740

    authors: Ratnoff OD,Everson B,Embury P,Ziats NP,Anderson JM,Emanuelson MM,Malemud CJ

    更新日期:1991-12-01 00:00:00

  • Nucleoporin MOS7/Nup88 is required for mitosis in gametogenesis and seed development in Arabidopsis.

    abstract::Angiosperm reproduction is characterized by alternate diploid sporophytic and haploid gametophytic generations. Gametogenesis shares similarities with that of animals except for the formation of the gametophyte, whereby haploid cells undergo several rounds of postmeiotic mitosis to form gametes and the accessory cells...

    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.1421911112

    authors: Park GT,Frost JM,Park JS,Kim TH,Lee JS,Oh SA,Twell D,Brooks JS,Fischer RL,Choi Y

    更新日期:2014-12-23 00:00:00

  • Structural determinants for membrane association and dynamic organization of the hepatitis C virus NS3-4A complex.

    abstract::Hepatitis C virus (HCV) NS3-4A is a membrane-associated multifunctional protein harboring serine protease and RNA helicase activities. It is an essential component of the HCV replication complex and a prime target for antiviral intervention. Here, we show that membrane association and structural organization of HCV NS...

    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.0807298105

    authors: Brass V,Berke JM,Montserret R,Blum HE,Penin F,Moradpour D

    更新日期:2008-09-23 00:00:00

  • Effects of binocular deprivation on the development of clustered horizontal connections in cat striate cortex.

    abstract::Intrinsic horizontal axon collaterals in the striate cortex of adult cats specifically link columns having the same preferred orientation; consequently, retrograde tracer injections result in intrinsic labeling that is sharply clustered. We have previously shown that the normal development of this circuitry involves t...

    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.88.3.745

    authors: Callaway EM,Katz LC

    更新日期:1991-02-01 00:00:00

  • Period determination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s).

    abstract::Daily rhythmic processes are coordinated by circadian clocks, which are present in numerous central and peripheral tissues. In mammals, two circadian clocks, the food-entrainable oscillator (FEO) and methamphetamine-sensitive circadian oscillator (MASCO), are "black box" mysteries because their anatomical loci are unk...

    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.1206213109

    authors: Pendergast JS,Oda GA,Niswender KD,Yamazaki S

    更新日期:2012-08-28 00:00:00

  • Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy.

    abstract::Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear....

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

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.1100349108

    authors: Hsu CS,Hsu SJ,Chen HC,Tseng TC,Liu CH,Niu WF,Jeng J,Liu CJ,Lai MY,Chen PJ,Kao JH,Chen DS

    更新日期:2011-03-01 00:00:00

  • Facebook language predicts depression in medical records.

    abstract::Depression, the most prevalent mental illness, is underdiagnosed and undertreated, highlighting the need to extend the scope of current screening methods. Here, we use language from Facebook posts of consenting individuals to predict depression recorded in electronic medical records. We accessed the history of Faceboo...

    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.1802331115

    authors: Eichstaedt JC,Smith RJ,Merchant RM,Ungar LH,Crutchley P,Preoţiuc-Pietro D,Asch DA,Schwartz HA

    更新日期:2018-10-30 00:00:00

  • How cytotoxic T cells manage to discriminate nonself from self at the nonapeptide level.

    abstract::Class I major histocompatibility complex (MHC) antigens are confronted with an apparently insurmountable dilemma. Each should show a binding preference to a common enough variety of nonapeptides, so that one relevant nonapeptide can be found in at least every other viral protein to provoke a cytotoxic T-cell response....

    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.89.10.4643

    authors: Ohno S

    更新日期:1992-05-15 00:00:00

  • delta-Aminolevulinic acid synthase from Euglena gracilis.

    abstract::delta-Aminolevulinic acid (ALA) synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] activity was detected in cell extracts of the unicellular green flagellate alga Euglena gracilis. The enzyme was identified by substrate and cofactor requirements, and activity was proportional to numbe...

    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.78.3.1666

    authors: Beale SI,Foley T,Dzelzkalns V

    更新日期:1981-03-01 00:00:00

  • Phosphocitrate inhibits mitochondrial and cytosolic accumulation of calcium in kidney cells in vivo.

    abstract::Synthetic 3-phosphocitrate, an extremely potent inhibitor of calcium phosphate crystallization as determined in a nonbiological physical-chemical assay, has many similarities to a mitochondrial factor that inhibits crystallization of nondiffracting amorphous calcium phosphate. In order to determine whether phosphocitr...

    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.78.9.5528

    authors: Tew WP,Malis CD,Howard JE,Lehninger AL

    更新日期:1981-09-01 00:00:00

  • Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene.

    abstract::Several mouse models have already proved valuable for investigating hypertrophic responses to cardiac stress. Here, we characterize one caused by a well defined single copy transgene, RenTgMK, that genetically clamps plasma renin and thence angiotensin II at high levels. All of the transgenic males develop concentric ...

    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.0307333101

    authors: Caron KM,James LR,Kim HS,Knowles J,Uhlir R,Mao L,Hagaman JR,Cascio W,Rockman H,Smithies O

    更新日期:2004-03-02 00:00:00