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Genomes and Genes | Gillian P BatesSummaryAffiliation: King's College London Country: UK Publications
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History of genetic disease: the molecular genetics of Huntington disease - a historyGillian P Bates
Department of Medical and Molecular Genetics, GKT School of Medicine, King s College London, 8th Floor Guy s Tower, Guy s Hospital, London SE1 9RT, United Kingdom
Nat Rev Genet 6:766-73. 2005..We are now equipped with powerful genetic models that continue to uncover new aspects of the pathogenesis of Huntington disease and will be instrumental for the development of therapeutic approaches for this disease...- BIOMEDICINE: One Misfolded Protein Allows Others to Sneak ByGillian P Bates
King's College London School of Medicine, London SE1 9RT, UK
Science 311:1385-6. 2006 
Suppression of protein aggregation by chaperone modification of high molecular weight complexesJohn Labbadia
Department of Medical and Molecular Genetics, King s College London, London SE1 9RT, UK
Brain 135:1180-96. 2012..Furthermore, our findings represent an important proof of principle that DNAJ manipulation is a valid therapeutic approach for intervention in Huntington's disease...- The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypesBen Woodman
Department of Medical and Molecular Genetics, King s College London School of Medicine, London, UK
Brain Res Bull 72:83-97. 2007..This supports the continued use of the more high-throughput fragment models to identify mechanisms of pathogenesis and for preclinical screening... - Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's diseaseCaroline L Benn
King s College London, Medical and Molecular Genetics, GKT School of Medicine, UK
Hum Mol Genet 14:3065-78. 2005..However, our data suggest that cytoplasmic mutant exon 1 htt, if present, contributes to disease progression... - Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington diseaseChristian Landles
Department Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London SE1 9RT, United Kingdom
J Biol Chem 285:8808-23. 2010..This methodology can be used to validate the inhibition of specific proteases as therapeutic targets for HD by pharmacological or genetic approaches... - Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's diseaseEmma Hockly
King's College London, Department of Medical and Molecular Genetics, GKT School of Medicine, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK
Neurobiol Dis 21:228-36. 2006..At the maximum tolerated dose, we achieved steady-state riluzole levels of 100 microM in brain. However, this was insufficient to inhibit aggregation in vivo and we found no improvement in the disease phenotype... - Genetic knock-down of HDAC7 does not ameliorate disease pathogenesis in the R6/2 mouse model of Huntington's diseaseCaroline L Benn
Department of Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London, UK
PLoS ONE 4:e5747. 2009..Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7... - Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activationAlexandra Zourlidou
Department of Medical and Molecular Genetics, King s College London, School of Medicine, London SE1 9RT, UK
Hum Mol Genet 16:1078-90. 2007..Our study is the first to suggest a differential modulation of Hsp27 activation in vivo and, importantly, it illustrates the diverse effect of Hsp27 on acute versus chronic models of disease... - Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's diseaseHilary Moffitt
Department of Medical and Molecular Genetics, King s College London School of Medicine, London, United Kingdom
PLoS ONE 4:e8025. 2009.... - The polyubiquitin Ubc gene modulates histone H2A monoubiquitylation in the R6/2 mouse model of Huntington's diseaseJohn S Bett
King s College London School of Medicine, Department of Medical and Molecular Genetics, King s College London, London, United Kingdom
J Cell Mol Med 13:2645-57. 2009..These results suggest that the expression of aggregation-prone mutant htt causes disturbances to the ubiquitin system, which may contribute to disease due to the diverse and important roles of ubiquitin... - Minocycline and doxycycline are not beneficial in a model of Huntington's diseaseDonna L Smith
Department of Medical and Molecular Genetics, King's College London, United Kingdom
Ann Neurol 54:186-96. 2003..In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline... - SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's diseaseMichal Mielcarek
Department of Medical and Molecular Genetics, King s College London, London, United Kingdom
PLoS ONE 6:e27746. 2011..We found that SAHA reduces SDS-insoluble aggregate load in the cortex and brain stem but not in the hippocampus of the R6/2 brains, and that this was accompanied by restoration of Bdnf cortical transcript levels... - Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's diseaseKirupa Sathasivam
Department of Medical and Molecular Genetics, King s College London School of Medicine, King s College London, 8th Floor Tower Wing, Guy s Tower, Great Maze Pond, London, UK
Hum Mol Genet 19:65-78. 2010.... - DNA instability in postmitotic neuronsRoman Gonitel
Department of Medical and Molecular Genetics, King s College London School of Medicine, London SE1 9RT, United Kingdom
Proc Natl Acad Sci U S A 105:3467-72. 2008.... - Proteasome impairment does not contribute to pathogenesis in R6/2 Huntington's disease mice: exclusion of proteasome activator REGgamma as a therapeutic targetJohn S Bett
Department of Medical and Molecular Genetics, GKT School of Medicine, King s College London, UK
Hum Mol Genet 15:33-44. 2006..These findings suggest that REGgamma is not a viable therapeutic target in polyglutamine disease and that overall proteasome function is not impaired by trapped mutant polyglutamine in R6/2 mice... - Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's diseaseAnna Bobrowska
Department of Medical and Molecular Genetics, King s College London, London, United Kingdom
PLoS ONE 6:e20696. 2011..Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD... - The ubiquitin-proteasome reporter GFPu does not accumulate in neurons of the R6/2 transgenic mouse model of Huntington's diseaseJohn S Bett
Department of Medical and Molecular Genetics, King s College London School of Medicine, King s College London, London, United Kingdom
PLoS ONE 4:e5128. 2009..It is therefore likely that the relationship between mutant polyglutamine proteins and the UPS is more complex than originally anticipated... - Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington diseaseJohn Labbadia
Department of Medical and Molecular Genetics, King s College London, London, UK
J Clin Invest 121:3306-19. 2011..Consequently, pharmacological induction of HSF1 as a therapeutic approach to HD is more complex than was previously anticipated... - Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approachDavid G Hay
Medical and Molecular Genetics, GKT School of Medicine, King's College, London, UK
Hum Mol Genet 13:1389-405. 2004..Radicicol and geldanamycin could both maintain chaperone induction for at least 3 weeks and alter the detergent soluble properties of polyQ aggregates over this time course... - Abnormal phosphorylation of synapsin I predicts a neuronal transmission impairment in the R6/2 Huntington's disease transgenic miceJean Charles Liévens
Medical and Molecular Genetics, GKT School of Medicine, London SE1 9RT, United Kingdom
Mol Cell Neurosci 20:638-48. 2002..Together the results suggest that an early impairment in synapsin phosphorylation-dephosphorylation may alter synaptic vesicle trafficking and lead to defective neurotransmission in HD... - Experimental therapeutics in Huntington's disease: are models useful for therapeutic trials?Gillian P Bates
King s College London, Guy s Hospital, London SE1 9RT, UK
Curr Opin Neurol 16:465-70. 2003..The role that disease models will play in this process is discussed... - Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's diseaseEmma Hockly
Medical and Molecular Genetics, Guy's, King's and St. Thomas' School of Medicine, King's College London, Eighth Floor Guy's Tower, Guy's Hospital, London SE1 9RT, United Kingdom
Proc Natl Acad Sci U S A 100:2041-6. 2003..SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics... - Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review seriesChristian Landles
Neurogenetics Laboratory, Medical and Molecular Genetics, GKT School of Medicine, King s College London, 8th Floor Guy s Tower, Guy s Hospital, London SE1 9RT, UK
EMBO Rep 5:958-63. 2004..We then focus on evidence that supports a role for transcriptional dysfunction and impaired protein folding and degradation as early events in disease pathogenesis... - Monitoring aggregate formation in organotypic slice cultures from transgenic miceDonna L Smith
Department of Medical and Molecular Genetics, GKT School of Medicine, King's College, Guy's Hospital, London, UK
Methods Mol Biol 277:161-71. 2004..This information is essential to the planning and application of an in vivo drug trial in the R6/2 mice... - Histone deacetylase inhibitors as therapeutics for polyglutamine disordersRachel Butler
King's College London School of Medicine, Department of Medical and Molecular Genetics, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK
Nat Rev Neurosci 7:784-96. 2006..Here, we discuss the potential therapeutic pathways through which histone deacetylase inhibitors might act to correct the aberrant transcription observed in Huntington's disease and other polyglutamine repeat diseases... - Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's diseaseLara Moumné
Department of Medical and Molecular Genetics, King s College London, London, United Kingdom
PLoS ONE 7:e31080. 2012..We conclude that HDAC3 should not be considered as the major mediator of the beneficial effect induced by SAHA and other HDAC inhibitors in HD... - Mouse models of triplet repeat diseasesGillian P Bates
King s College London, Department of Medical and Molecular Genetics, GKT School of Medicine, 8th Floor Guy s Tower, Guy s Hospital, London SE1 9RT, United Kingdom
Mol Biotechnol 32:147-58. 2006.... - Mouse models of triplet repeat diseasesGillian P Bates
Department of Medical and Molecular Genetics, GKT School of Medicine, King's College, Guy's Hospital, London, UK
Methods Mol Biol 277:3-15. 2004..Mouse models have proved extremely useful in these goals and are now also being used for the preclinical testing of therapeutic compounds. This chapter reviews the successes and limitations of the approaches that have been developed... - Optimisation of region-specific reference gene selection and relative gene expression analysis methods for pre-clinical trials of Huntington's diseaseCaroline L Benn
Medical and Molecular Genetics, King s College London School of Medicine, 8th Floor Tower Wing, Guy s Hospital, Great Maze Pond, London, SE1 9RT, UK
Mol Neurodegener 3:17. 2008..To remedy this situation, 12 housekeeping genes were examined to identify suitable reference genes for use in expression assays... - Environmental enrichment slows disease progression in R6/2 Huntington's disease miceEmma Hockly
Division of Medical and Molecular Genetics, GKT School of Medicine, King s College London, UK
Ann Neurol 51:235-42. 2002..Enrichment also delayed the loss of peristriatal cerebral volume in R6/2 brains. These results could provide the basis for a rational approach to ameliorate the effects of Huntington's disease... - Arfaptin 2 regulates the aggregation of mutant huntingtin proteinPeter J Peters
Division of Tumor Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Nat Cell Biol 4:240-5. 2002..Our data suggest that arfaptin 2 is involved in regulating huntingtin protein aggregation, possibly by impairing proteasome function... - Sensitive biochemical aggregate detection reveals aggregation onset before symptom development in cellular and murine models of Huntington's diseaseAndreas Weiss
Neuroscience Discovery, Novartis Institutes for BioMedical Research, Basel, Switzerland
J Neurochem 104:846-58. 2008.... - Increased metabolism in the R6/2 mouse model of Huntington's diseaseJorien M M van der Burg
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University BMC A10, Lund, Sweden
Neurobiol Dis 29:41-51. 2008..Together, these data demonstrate that weight loss in R6/2 mice is associated with increased metabolism and changes in several weight-regulating factors... - Global changes to the ubiquitin system in Huntington's diseaseEric J Bennett
Department of Biological Sciences, Stanford University, Stanford, California 94305, USA
Nature 448:704-8. 2007..Thus, HD is linked to global changes in the ubiquitin system to a much greater extent than previously recognized... - A potent small molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration in vivoXiaoqian Zhang
Department of Biochemistry, Boston University Medical School, Boston, MA 02118, USA
Proc Natl Acad Sci U S A 102:892-7. 2005..The aggregation inhibitors identified in this screen represent four primary chemical scaffolds and are strong lead compounds for the development of therapeutics for human polyQ diseases... - A human single-chain Fv intrabody preferentially targets amino-terminal Huntingtin's fragments in striatal models of Huntington's diseaseTodd W Miller
Division of Genetic Disorders Wadsworth Center, New York State Department of Health, and Department of Biomedical Sciences, University at Albany, NY 12208, USA
Neurobiol Dis 19:47-56. 2005..Intrabodies may be used as potential curative agents, and as drug discovery tools, for HD and other misfolded protein disorders... - Depletion of rabphilin 3A in a transgenic mouse model (R6/1) of Huntington's disease, a possible culprit in synaptic dysfunctionRuben Smith
Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden
Neurobiol Dis 20:673-84. 2005..Our results indicate that a decrease in mRNA levels underlie the depletion of protein levels of rabphilin 3A, and we suggest that this reduction may be involved in causing impaired synaptic transmission in R6/1 mice... - Reduction of GnRH and infertility in the R6/2 mouse model of Huntington's diseaseEugenia Papalexi
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, BMC A10, 221 84 Lund, Sweden
Eur J Neurosci 22:1541-6. 2005..Gonadotropic hormone replacement did not mitigate weight loss or restore motor function in R6/2 males... - Metabolic characterization of the R6/2 transgenic mouse model of Huntington's disease by high-resolution MAS 1H NMR spectroscopyTsz M Tsang
Biological Chemistry, Biomedical Sciences Division, Faculty of Medicine, Imperial College, London, SW7 2AZ, United Kingdom
J Proteome Res 5:483-92. 2006..Clear differentiation of R6/2 and wild-type mice was also obtained for urine and blood metabolite profiles that may have applicability for monitoring HD in human populations... - Complex alteration of NMDA receptors in transgenic Huntington's disease mouse brain: analysis of mRNA and protein expression, plasma membrane association, interacting proteins, and phosphorylationRuth Luthi-Carter
MassGeneral Institute for Neurodegenerative Diseases, B114-2000, 114 16th Street, Charlestown, MA 02129-4404, USA
Neurobiol Dis 14:624-36. 2003..Taken together, these data demonstrate multiple levels of NMDA receptor dysregulation, including abnormalities in mRNA expression levels, receptor stoichiometry, protein phosphorylation, and receptor trafficking... - Progressive alterations in the hypothalamic-pituitary-adrenal axis in the R6/2 transgenic mouse model of Huntington's diseaseMaria Björkqvist
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, BMC A10, Lund, Sweden
Hum Mol Genet 15:1713-21. 2006..This progressive increase in cortisol may contribute to the clinical symptoms, such as muscular wasting, mood changes and some of the cognitive deficits that occur in HD... - Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease micePaolo Guidetti
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA
Neurobiol Dis 23:190-7. 2006.... - Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosageAlexandre Kuhn
Ecole Polytechnique Federale de Lausanne EPFL, 1015 Lausanne, Switzerland
Hum Mol Genet 16:1845-61. 2007.... - A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's diseaseMaria Björkqvist
Neuronal Survival Unit, Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, S 221 00 Lund, Sweden
J Exp Med 205:1869-77. 2008..Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD... - Alterations in the mouse and human proteome caused by Huntington's diseaseClaus Zabel
, , 13353 Berlin, Germany
Mol Cell Proteomics 1:366-75. 2002..Maintaining alpha1-antitrypsin and alphaB-crystallin availability during the course of Huntington's disease might prevent neuronal cell death and therefore could be useful in delaying the disease progression... - Biomarkers for neurodegenerative diseasesSusie M D Henley
Dementia Research Centre, Institute of Neurology, University College London, London, UK
Curr Opin Neurol 18:698-705. 2005..This review summarizes the field of biomarker research in the major neurodegenerative diseases... - Polyglutamine expansion of huntingtin impairs its nuclear exportJonathan Cornett
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA
Nat Genet 37:198-204. 2005..These results suggest that Tpr has a role in the nuclear export of N-terminal htt and that polyQ expansion reduces this nuclear export to cause the nuclear accumulation of htt... - Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidatesAnnette Dalrymple
Proteome Sciences plc, Cobham, Surrey, United Kingdom
J Proteome Res 6:2833-40. 2007..Proteins of interest were evaluated using immunoblotting and ELISA in plasma from 2 populations, CSF and R6/2 mice. The identified proteins demonstrate neuroinflammation in HD and warrant further investigation as possible biomarkers...