当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > Myricetin Reduces Toxic Level of CAG Repeats RNA in Huntington's Disease (HD) and Spino Cerebellar Ataxia (SCAs).

Myricetin Reduces Toxic Level of CAG Repeats RNA in Huntington's Disease (HD) and Spino Cerebellar Ataxia (SCAs).

Abstract：

:Huntington's disease (HD) is a neurodegenerative disorder that is caused by abnormal expansion of CAG repeats in the HTT gene. The transcribed mutant RNA contains expanded CAG repeats that translate into a mutant huntingtin protein. This expanded CAG repeat also causes mis-splicing of pre-mRNA due to sequestration of muscle blind like-1 splicing factor (MBNL1), and thus both of these elicit the pathogenesis of HD. Targeting the onset as well as progression of HD by small molecules could be a potent therapeutic approach. We have screened a set of small molecules to target this transcript and found Myricetin, a flavonoid, as a lead molecule that interacts with the CAG motif and thus prevents the translation of mutant huntingtin protein as well as sequestration of MBNL1. Here, we report the first solution structure of the complex formed between Myricetin and RNA containing the 5'CAG/3'GAC motif. Myricetin interacts with this RNA via base stacking at the AA mismatch. Moreover, Myricetin was also found reducing the proteo-toxicity generated due to the aggregation of polyglutamine, and further, its supplementation also improves neurobehavioral deficits in the HD mouse model. Our study provides the structural and mechanistic basis of Myricetin as an effective therapeutic candidate for HD and other polyQ related disorders.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Khan E,Tawani A,Mishra SK,Verma AK,Upadhyay A,Kumar M,Sandhir R,Mishra A,Kumar A

doi

10.1021/acschembio.7b00699

subject

Has Abstract

pub_date

2018-01-19 00:00:00

pages

180-188

issue

1

eissn

1554-8929

issn

1554-8937

journal_volume

13

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • Insertions within the Saxitoxin Biosynthetic Gene Cluster Result in Differential Toxin Profiles.

    abstract：:The neurotoxin saxitoxin and related paralytic shellfish toxins are produced by multiple species of cyanobacteria and dinoflagellates. This study investigates the two saxitoxin-producing strains of Scytonema crispum, CAWBG524 and CAWBG72, isolated in New Zealand. Each strain was previously reported to have a distinct ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00608

    authors： Cullen A,D'Agostino PM,Mazmouz R,Pickford R,Wood S,Neilan BA

    更新日期：2018-11-16 00:00:00

  • Antagonists for Constitutively Active Mutant Estrogen Receptors: Insights into the Roles of Antiestrogen-Core and Side-Chain.

    abstract：:A major risk for patients having estrogen receptor α (ERα)-positive breast cancer is the recurrence of drug-resistant metastases after initial successful treatment with endocrine therapies. Recent studies have implicated a number of activating mutations in the ligand-binding domain of ERα that stabilize the agonist co...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00877

    authors： Sharma A,Toy W,Guillen VS,Sharma N,Min J,Carlson KE,Mayne CG,Lin S,Sabio M,Greene G,Katzenellenbogen BS,Chandarlapaty S,Katzenellenbogen JA

    更新日期：2018-12-21 00:00:00

  • Bacterial evolution by intelligent design.

    abstract：:In a process called quorum sensing, bacteria produce and secrete certain signaling compounds (called autoinducers) that bind to receptors on other bacteria and activate transcription of certain genes. A clever genetic selection yields a new quorum-sensing transcriptional regulator that marches to the beat of a differe...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb6003417

    authors： Winans SC

    更新日期：2006-08-22 00:00:00

  • Profiling heparin-chemokine interactions using synthetic tools.

    abstract：:Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyt...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb700159m

    authors： de Paz JL,Moseman EA,Noti C,Polito L,von Andrian UH,Seeberger PH

    更新日期：2007-11-20 00:00:00

  • Heterologous Biosynthesis of Type II Polyketide Products Using E. coli.

    abstract：:The heterologous biosynthesis of complex natural products has enabled access to polyketide, nonribosomal peptide, isoprenoid, and other compounds with wide-spanning societal value. Though several surrogate host systems exist, Escherichia coli is often a preferred choice due to its rapid growth kinetics and extensive m...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00827

    authors： Liu X,Hua K,Liu D,Wu ZL,Wang Y,Zhang H,Deng Z,Pfeifer BA,Jiang M

    更新日期：2020-05-15 00:00:00

  • Novel inhibitors of human DOPA decarboxylase extracted from Euonymus glabra Roxb.

    abstract：:Dopamine, a biogenic amine with important biological functions, is produced from l-DOPA by DOPA decarboxylase (DDC). DDC is a potential target to modulate the production of dopamine in several pathological states. Known inhibitors of DDC have been used for treatment of Parkinson's disease but suffered low specificity ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb500009r

    authors： Ren J,Zhang Y,Jin H,Yu J,Zhou Y,Wu F,Zhang W

    更新日期：2014-04-18 00:00:00

  • Discovery of a nitric oxide responsive quorum sensing circuit in Vibrio harveyi.

    abstract：:Bacteria use small molecules to assess the density and identity of nearby organisms and formulate a response. This process, called quorum sensing (QS), commonly regulates bioluminescence, biofilm formation, and virulence. Vibrio harveyi have three described QS circuits. Each involves the synthesis of a molecule that r...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300215t

    authors： Henares BM,Higgins KE,Boon EM

    更新日期：2012-08-17 00:00:00

  • Chemical detoxification of small molecules by Caenorhabditis elegans.

    abstract：:Caenorhabditis elegans lives in compost and decaying fruit, eats bacteria and is exposed to pathogenic microbes. We show that C. elegans is able to modify diverse microbial small-molecule toxins via both O- and N-glucosylation as well as unusual 3'-O-phosphorylation of the resulting glucosides. The resulting glucosyla...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300520u

    authors： Stupp GS,von Reuss SH,Izrayelit Y,Ajredini R,Schroeder FC,Edison AS

    更新日期：2013-02-15 00:00:00

  • Diverse Class 2 CRISPR-Cas Effector Proteins for Genome Engineering Applications.

    abstract：:CRISPR-Cas genome editing technologies have revolutionized modern molecular biology by making targeted DNA edits simple and scalable. These technologies are developed by domesticating naturally occurring microbial adaptive immune systems that display wide diversity of functionality for targeted nucleic acid cleavage. ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/acschembio.7b00800

    authors： Pyzocha NK,Chen S

    更新日期：2018-02-16 00:00:00

  • Rational Design of a Dephosphorylation-Resistant Reporter Enables Single-Cell Measurement of Tyrosine Kinase Activity.

    abstract：:Although peptide-based reporters of protein tyrosine kinase (PTK) activity have been used to study PTK enzymology in vitro, the application of these reporters to intracellular conditions is compromised by their dephosphorylation, preventing PTK activity measurements. Nonproteinogenic amino acids may be utilized to rat...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00667

    authors： Turner AH,Lebhar MS,Proctor A,Wang Q,Lawrence DS,Allbritton NL

    更新日期：2016-02-19 00:00:00

  • Formylglycine, a post-translationally generated residue with unique catalytic capabilities and biotechnology applications.

    abstract：:Formylglycine (fGly) is a catalytically essential residue found almost exclusively in the active sites of type I sulfatases. Formed by post-translational oxidation of cysteine or serine side chains, this aldehyde-functionalized residue participates in a unique and highly efficient catalytic mechanism for sulfate ester...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb500897w

    authors： Appel MJ,Bertozzi CR

    更新日期：2015-01-16 00:00:00

  • Structure-Based Mutagenesis of Phycobiliprotein smURFP for Optoacoustic Imaging.

    abstract：:Photo- or optoacoustics (OA) imaging is increasingly being used as a non-invasive imaging method that can simultaneously reveal structure and function in deep tissue. However, the most frequent transgenic OA labels are current fluorescent proteins that are not optimized for OA imaging. Thus, they lack OA signal streng...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00299

    authors： Fuenzalida Werner JP,Mishra K,Huang Y,Vetschera P,Glasl S,Chmyrov A,Richter K,Ntziachristos V,Stiel AC

    更新日期：2019-09-20 00:00:00

  • Small molecule inhibitors of bromodomain-acetyl-lysine interactions.

    abstract：:Bromodomains are protein modules that bind to acetylated lysine residues. Their interaction with histone proteins suggests that they function as "readers" of histone lysine acetylation, a component of the proposed "histone code". Bromodomain-containing proteins are often found as components of larger protein complexes...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb500996u

    authors： Brand M,Measures AR,Wilson BG,Cortopassi WA,Alexander R,Höss M,Hewings DS,Rooney TP,Paton RS,Conway SJ

    更新日期：2015-01-16 00:00:00

  • Functional and Structural Insights into a Novel Promiscuous Ketoreductase of the Lugdunomycin Biosynthetic Pathway.

    abstract：:Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (1), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthe...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00564

    authors： Xiao X,Elsayed SS,Wu C,van der Heul HU,Metsä-Ketelä M,Du C,Prota AE,Chen CC,Liu W,Guo RT,Abrahams JP,van Wezel GP

    更新日期：2020-09-18 00:00:00

  • Identification of a Novel Mycobacterial Arabinosyltransferase Activity Which Adds an Arabinosyl Residue to α-d-Mannosyl Residues.

    abstract：:The arabinosyltransferases responsible for the biosynthesis of the arabinan domains of two abundant heteropolysaccharides of the cell envelope of all mycobacterial species, lipoarabinomannan and arabinogalactan, are validated drug targets. Using a cell envelope preparation from Mycobacterium smegmatis as the enzyme so...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00093

    authors： Angala SK,McNeil MR,Zou L,Liav A,Zhang J,Lowary TL,Jackson M

    更新日期：2016-06-17 00:00:00

  • Bacterial β-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2).

    abstract：:Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceram...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00192

    authors： Charoenwattanasatien R,Pengthaisong S,Breen I,Mutoh R,Sansenya S,Hua Y,Tankrathok A,Wu L,Songsiriritthigul C,Tanaka H,Williams SJ,Davies GJ,Kurisu G,Cairns JR

    更新日期：2016-07-15 00:00:00

  • Bioactivity-HiTES Unveils Cryptic Antibiotics Encoded in Actinomycete Bacteria.

    abstract：:Bacteria harbor an immense reservoir of potentially new and therapeutic small molecules in the form of "silent" biosynthetic gene clusters (BGCs). These BGCs can be identified bioinformatically but are sparingly expressed under normal laboratory growth conditions, or not at all, and therefore do not produce significan...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00049

    authors： Moon K,Xu F,Zhang C,Seyedsayamdost MR

    更新日期：2019-04-19 00:00:00

  • Botryllamides: natural product inhibitors of ABCG2.

    abstract：:ABCG2 is a membrane-localized, human transporter protein that has been demonstrated to reduce the intracellular accumulation of substrates through ATP-dependent efflux. Highly expressed in placental syncytiotrophoblasts, brain microvasculature, and the gastrointestinal tract, ABCG2 has been shown to mediate normal tis...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900134c

    authors： Henrich CJ,Robey RW,Takada K,Bokesch HR,Bates SE,Shukla S,Ambudkar SV,McMahon JB,Gustafson KR

    更新日期：2009-08-21 00:00:00

  • Traceless labeling of glycoproteins and its application to the study of glycoprotein-protein interactions.

    abstract：:A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400631w

    authors： Yang YL,Lee YP,Yang YL,Lin PC

    更新日期：2014-02-21 00:00:00

  • Cyanopyrrolidine Inhibitors of Ubiquitin Specific Protease 7 Mediate Desulfhydration of the Active-Site Cysteine.

    abstract：:Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of elect...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00031

    authors： Bashore C,Jaishankar P,Skelton NJ,Fuhrmann J,Hearn BR,Liu PS,Renslo AR,Dueber EC

    更新日期：2020-06-19 00:00:00

  • Detecting Secretory Proteins by Acoustic Droplet Ejection in Multiplexed High-Throughput Applications.

    abstract：:Nearly one-third of the encoded proteome is comprised of secretory proteins that enable communication between cells and organ systems, playing a ubiquitous role in human health and disease. High-throughput detection of secreted proteins would enhance efforts to identify therapies for secretion-related diseases. Using ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00001

    authors： Iannotti MJ,MacArthur R,Jones R,Tao D,Singeç I,Michael S,Inglese J

    更新日期：2019-03-15 00:00:00

  • Structural Chemistry of Human RNA Methyltransferases.

    abstract：:RNA methyltransferases (RNMTs) play important roles in RNA stability, splicing, and epigenetic mechanisms. They constitute a promising target class that is underexplored by the medicinal chemistry community. Information of relevance to drug design can be extracted from the rich structural coverage of human RNMTs. In t...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00781

    authors： Schapira M

    更新日期：2016-03-18 00:00:00

  • Humanized Lewis-Y specific antibody based delivery of STAT3 siRNA.

    abstract：:The clinical application of siRNA is limited largely by the lack of efficient, cell-specific delivery systems. Antibodies are attractive delivery vehicles for targeted therapy due to their high specificity. In this study we describe the use of a humanized monoclonal antibody (mAb), hu3S193, against Lewis-Y (Le(y)), as...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200176v

    authors： Ma Y,Kowolik CM,Swiderski PM,Kortylewski M,Yu H,Horne DA,Jove R,Caballero OL,Simpson AJ,Lee FT,Pillay V,Scott AM

    更新日期：2011-09-16 00:00:00

  • Evaluation of analogues of GalNAc as substrates for enzymes of the mammalian GalNAc salvage pathway.

    abstract：:Changes in glycosylation are correlated to disease and associated with differentiation processes. Experimental tools are needed to investigate the physiological implications of these changes either by labeling of the modified glycans or by blocking their biosynthesis. N-Acetylgalactosamine (GalNAc) is a monosaccharide...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb200511t

    authors： Pouilly S,Bourgeaux V,Piller F,Piller V

    更新日期：2012-04-20 00:00:00

  • Stepwise Loop Insertion Strategy for Active Site Remodeling to Generate Novel Enzyme Functions.

    abstract：:The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used t...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00018

    authors： Hoque MA,Zhang Y,Chen L,Yang G,Khatun MA,Chen H,Hao L,Feng Y

    更新日期：2017-05-19 00:00:00

  • Biocatalytic Detoxification of Paralytic Shellfish Toxins.

    abstract：:Small molecules that bind to voltage-gated sodium channels (VGSCs) are promising leads in the treatment of numerous neurodegenerative diseases and pain. Nature is a highly skilled medicinal chemist in this regard, designing potent VGSC ligands capable of binding to and blocking the channel, thereby offering compounds ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.9b00123

    authors： Lukowski AL,Denomme N,Hinze ME,Hall S,Isom LL,Narayan ARH

    更新日期：2019-05-17 00:00:00

  • Comparative chemogenomics to examine the mechanism of action of dna-targeted platinum-acridine anticancer agents.

    abstract：:Platinum-based drugs have been used to successfully treat diverse cancers for several decades. Cisplatin, the original compound of this class, cross-links DNA, resulting in cell cycle arrest and cell death via apoptosis. Cisplatin is effective against several tumor types, yet it exhibits toxic side effects and tumors ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300320d

    authors： Cheung-Ong K,Song KT,Ma Z,Shabtai D,Lee AY,Gallo D,Heisler LE,Brown GW,Bierbach U,Giaever G,Nislow C

    更新日期：2012-11-16 00:00:00

  • EcoSynther: A Customized Platform To Explore the Biosynthetic Potential in E. coli.

    abstract：:Developing computational tools for a chassis-centered biosynthetic pathway design is very important for a productive heterologous biosynthesis system by considering enormous foreign biosynthetic reactions. For many cases, a pathway to produce a target molecule consists of both native and heterologous reactions when ut...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00605

    authors： Ding S,Liao X,Tu W,Wu L,Tian Y,Sun Q,Chen J,Hu QN

    更新日期：2017-11-17 00:00:00

  • Cell Permeable Ratiometric Fluorescent Sensors for Imaging Phosphoinositides.

    abstract：:Phosphoinositides are critical cell-signal mediators present on the plasma membrane. The dynamic change of phosphoinositide concentrations on the membrane including clustering and declustering mediates signal transduction. The importance of phosphoinositides is scored by the fact that they participate in almost all ce...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00067

    authors： Mondal S,Rakshit A,Pal S,Datta A

    更新日期：2016-07-15 00:00:00

  • Engineering Atypical Tetracycline Formation in Amycolatopsis sulphurea for the Production of Modified Chelocardin Antibiotics.

    abstract：:To combat the increasing spread of antimicrobial resistance and the shortage of novel anti-infectives, one strategy for the development of new antibiotics is to optimize known chemical scaffolds. Here, we focus on the biosynthetic engineering of Amycolatopsis sulphurea for derivatization of the atypical tetracycline c...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b01125

    authors： Lukežič T,Fayad AA,Bader C,Harmrolfs K,Bartuli J,Groß S,Lešnik U,Hennessen F,Herrmann J,Pikl Š,Petković H,Müller R

    更新日期：2019-03-15 00:00:00