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.
journal_name
Proc Natl Acad Sci U S Aauthors
Jang SW,Liu X,Yepes M,Shepherd KR,Miller GW,Liu Y,Wilson WD,Xiao G,Blanchi B,Sun YE,Ye Kdoi
10.1073/pnas.0913572107subject
Has Abstractpub_date
2010-02-09 00:00:00pages
2687-92issue
6eissn
0027-8424issn
1091-6490pii
0913572107journal_volume
107pub_type
杂志文章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
更新日期:2004-05-11 00:00:00
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
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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
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更新日期:1999-02-16 00:00:00
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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
更新日期:2002-06-11 00:00:00
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
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doi:10.1073/pnas.71.12.5088
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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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
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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
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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
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更新日期:1977-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2020-09-22 00:00:00
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
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更新日期:2020-11-24 00:00:00
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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
更新日期:2015-05-19 00:00:00
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
更新日期:2002-02-05 00:00:00
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
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更新日期:1986-02-01 00:00:00
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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
更新日期:1985-01-01 00:00:00
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
更新日期:2017-07-11 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2009-05-26 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2014-12-23 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2008-09-23 00:00:00
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
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更新日期:1991-02-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2012-08-28 00:00:00
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
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更新日期:2011-03-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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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
更新日期:1992-05-15 00:00:00
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
更新日期:1981-03-01 00:00:00
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
更新日期:1981-09-01 00:00:00
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
更新日期:2004-03-02 00:00:00