Experimental therapeutics in transgenic mouse models of Huntington's disease

Despite important advances in understanding and elucidating the molecular and mechanistic pathways that mediate progression in Huntington's disease (HD), effective pharmacotherapy remains elusive. Insights into disease pathogenesis have come from studies using tissue culture, yeast, Caenorhabditis elegans, Drosophila melanogaster and transgenic mouse models. Here, we present a brief overview of HD pathogenesis and discuss the efficacy of therapeutic agents in transgenic mouse models of HD. We conclude by considering issues that affect the translation of findings in transgenic mouse models of HD to human clinical trials.

[1]  J. Martell,et al.  Chorea , 1954, The Canadian nurse.

[2]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[3]  B. Hyman,et al.  Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  B. Rosen,et al.  Evidence for irnnairment of energy metabofism in vivo in Huntington's disease using localized 1H NMR spectroscopy , 1993, Neurology.

[5]  B R Rosen,et al.  Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. , 1993, Neurology.

[6]  B. Rosen,et al.  Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate , 1994, Annals of neurology.

[7]  W. Augustin,et al.  Relations between tocopherol depletion and coenzyme Q during lipid peroxidation in rat liver mitochondria. , 1994, Free radical research.

[8]  M. Beal,et al.  Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. W. Davies,et al.  Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice , 1996, Cell.

[10]  S. Bassett,et al.  Long-term treatment of girls with ornithine transcarbamylase deficiency. , 1996, The New England journal of medicine.

[11]  M. Hayden,et al.  Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract , 1996, Nature Genetics.

[12]  J. Cooper,et al.  Mitochondrial defect in Huntington's disease caudate nucleus , 1996, Annals of neurology.

[13]  B. Rosen,et al.  Energy metabolism defects in Huntington's disease and effects of coenzyme Q10 , 1997, Annals of neurology.

[14]  A. Roses,et al.  Transglutaminase-catalyzed inactivation of glyceraldehyde 3-phosphate dehydrogenase and alpha-ketoglutarate dehydrogenase complex by polyglutamine domains of pathological length. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Beal,et al.  Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia , 1997, Annals of neurology.

[16]  S. Tsuji,et al.  Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch , 1998, Nature Genetics.

[17]  H. Green,et al.  Transglutaminase action imitates Huntington's disease: selective polymerization of Huntingtin containing expanded polyglutamine. , 1998, Molecular cell.

[18]  J. Blass,et al.  Tissue transglutaminase-catalyzed formation of high-molecular-weight aggregates in vitro is favored with long polyglutamine domains: a possible mechanism contributing to CAG-triplet diseases. , 1998, Archives of biochemistry and biophysics.

[19]  Lisa Garrett,et al.  Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA , 1998, Nature Genetics.

[20]  A. Morton,et al.  Striatal Transplantation in a Transgenic Mouse Model of Huntington's Disease , 1998, Experimental Neurology.

[21]  Bruce R. Rosen,et al.  Neuroprotective Effects of Creatine and Cyclocreatine in Animal Models of Huntington’s Disease , 1998, The Journal of Neuroscience.

[22]  J. M. Boutell,et al.  Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin. , 1999, Human molecular genetics.

[23]  H. Johnston,et al.  A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. , 1999, Human molecular genetics.

[24]  S. Snyder,et al.  Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization , 1999, Nature Medicine.

[25]  J. Blenis,et al.  Caspase-8 Is Required for Cell Death Induced by Expanded Polyglutamine Repeats , 1999, Neuron.

[26]  J. D. de Yébenes,et al.  Clinical correlation of striatal 1H MRS changes in Huntington’s disease , 1999, Neurology.

[27]  D. Borchelt,et al.  Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. , 1999, Human molecular genetics.

[28]  J. Penney,et al.  Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease , 1999, Nature.

[29]  D. Housman,et al.  Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  O. Hansson,et al.  Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Beal,et al.  Oxidative Stress in Huntington's Disease , 1999, Brain pathology.

[32]  D. Price,et al.  Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington's disease brain nuclei. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. Ferrante,et al.  Tissue Transglutaminase Is Increased in Huntington's Disease Brain , 1999, Journal of neurochemistry.

[34]  D. Housman,et al.  The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. MacDonald,et al.  Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. , 2000, Human molecular genetics.

[36]  Colin Blakemore,et al.  Delaying the onset of Huntington's in mice , 2000, Nature.

[37]  C A Ross,et al.  Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. , 2000, Human molecular genetics.

[38]  C. Ríos,et al.  Striatal oxidative damage parallels the expression of a neurological phenotype in mice transgenic for the mutation of Huntington’s disease , 2000, Brain Research.

[39]  Ole A. Andreassen,et al.  Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease , 2000, The Journal of Neuroscience.

[40]  René Hen,et al.  Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's Disease , 2000, Cell.

[41]  S. Hersch,et al.  Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease , 2000, Nature Medicine.

[42]  A. Morton,et al.  Environmental stimulation increases survival in mice transgenic for exon 1 of the Huntington's disease gene , 2000, Movement disorders : official journal of the Movement Disorder Society.

[43]  D. Manners,et al.  Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy , 2000, Annals of neurology.

[44]  Y. Kawaoka,et al.  Epidermal immunization by a needle-free powder delivery technology: Immunogenicity of influenza vaccine and protection in mice , 2000, Nature Medicine.

[45]  R. Nussbaum,et al.  Neurodegeneration in the polyglutamine diseases: Act 1, Scene 1 , 2000, Nature Neuroscience.

[46]  Huda Y. Zoghbi,et al.  Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1 , 2000, Nature Neuroscience.

[47]  S. W. Davies,et al.  Transgenic Mouse Models of Huntington’s Disease , 2000 .

[48]  A H Schapira,et al.  Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse , 2000, Annals of neurology.

[49]  S. W. Davies,et al.  Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Scarpulla,et al.  Sequential Serum-dependent Activation of CREB and NRF-1 Leads to Enhanced Mitochondrial Respiration through the Induction of Cytochrome c * , 2000, The Journal of Biological Chemistry.

[51]  I. Kanazawa,et al.  Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription , 2000, Nature Genetics.

[52]  K. Fischbeck,et al.  CREB-binding protein sequestration by expanded polyglutamine. , 2000, Human molecular genetics.

[53]  A. Deckel,et al.  Reduced activity and protein expression of NOS in R6/2 HD transgenic mice: effects of l-NAME on symptom progression , 2001, Brain Research.

[54]  C. Blakemore,et al.  Anterior cingulate cortical transplantation in transgenic Huntington’s disease mice , 2001, Brain Research Bulletin.

[55]  A. Burlina,et al.  Long-term treatment with sodium phenylbutyrate in ornithine transcarbamylase-deficient patients. , 2001, Molecular genetics and metabolism.

[56]  C. Ware,et al.  Polyglutamine-Expanded Ataxin-7 Antagonizes CRX Function and Induces Cone-Rod Dystrophy in a Mouse Model of SCA7 , 2001, Neuron.

[57]  H. Lehrach,et al.  Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. , 2001, Human molecular genetics.

[58]  O. Hansson,et al.  Partial resistance to malonate‐induced striatal cell death in transgenic mouse models of Huntington's disease is dependent on age and CAG repeat length , 2001, Journal of neurochemistry.

[59]  I. Fridovich,et al.  Neuroprotection from Delayed Postischemic Administration of a Metalloporphyrin Catalytic Antioxidant , 2001, The Journal of Neuroscience.

[60]  O. Andreassen,et al.  Creatine Increases Survival and Delays Motor Symptoms in a Transgenic Animal Model of Huntington's Disease , 2001, Neurobiology of Disease.

[61]  A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington’s disease , 2001, Neurology.

[62]  F. Gage,et al.  Identities of Sequestered Proteins in Aggregates from Cells with Induced Polyglutamine Expression , 2001, The Journal of cell biology.

[63]  O. Andreassen,et al.  Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease , 2001, Journal of neurochemistry.

[64]  P G Bhide,et al.  Early and Progressive Accumulation of Reactive Microglia in the Huntington Disease Brain , 2001, Journal of neuropathology and experimental neurology.

[65]  M. Beal,et al.  N ε ‐(γ‐l‐Glutamyl)‐l‐lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington's disease , 2001 .

[66]  C A Ross,et al.  Interference by Huntingtin and Atrophin-1 with CBP-Mediated Transcription Leading to Cellular Toxicity , 2001, Science.

[67]  Z. Qin,et al.  Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington's disease brains, associate with membranes, and undergo calpain-dependent proteolysis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  H Li,et al.  Huntingtin Aggregate-Associated Axonal Degeneration is an Early Pathological Event in Huntington's Disease Mice , 2001, The Journal of Neuroscience.

[69]  O. Andreassen,et al.  Lipoic acid improves survival in transgenic mouse models of Huntington's disease , 2001, Neuroreport.

[70]  O. Andreassen,et al.  Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease , 2001, Annals of neurology.

[71]  K. Fischbeck,et al.  Histone deacetylase inhibitors reduce polyglutamine toxicity , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[72]  R. Albin,et al.  Neurological abnormalities in a knock-in mouse model of Huntington's disease. , 2001, Human molecular genetics.

[73]  O. Andreassen,et al.  Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. , 2001, Neurobiology of disease.

[74]  D. Borchelt,et al.  Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model , 2001, Neuroscience Letters.

[75]  D. Housman,et al.  Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila , 2001, Nature.

[76]  Blair R. Leavitt,et al.  Caspase Cleavage of Mutant Huntingtin Precedes Neurodegeneration in Huntington's Disease , 2002, The Journal of Neuroscience.

[77]  J. Olson,et al.  Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease. , 2002, Human molecular genetics.

[78]  R. Wetzel,et al.  Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. , 2002, Human molecular genetics.

[79]  Joel S Perlmutter,et al.  Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. , 2002, Archives of neurology.

[80]  J. Schiefer,et al.  Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntington's disease , 2002, Movement disorders : official journal of the Movement Disorder Society.

[81]  He Li,et al.  Interaction of Huntington Disease Protein with Transcriptional Activator Sp1 , 2002, Molecular and Cellular Biology.

[82]  P. Brundin,et al.  Maintenance of Susceptibility to Neurodegeneration Following Intrastriatal Injections of Quinolinic Acid in a New Transgenic Mouse Model of Huntington's Disease , 2002, Experimental Neurology.

[83]  Ole A. Andreassen,et al.  Therapeutic Effects of Coenzyme Q10 and Remacemide in Transgenic Mouse Models of Huntington's Disease , 2002, The Journal of Neuroscience.

[84]  D. Housman,et al.  A bivalent Huntingtin binding peptide suppresses polyglutamine aggregation and pathogenesis in Drosophila , 2002, Nature Genetics.

[85]  A. Deckel,et al.  Altered neuronal nitric oxide synthase expression contributes to disease progression in Huntington’s disease transgenic mice , 2002, Brain Research.

[86]  C. Steer,et al.  Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[87]  M. Chesselet,et al.  Early Motor Dysfunction and Striosomal Distribution of Huntingtin Microaggregates in Huntington's Disease Knock-In Mice , 2002, The Journal of Neuroscience.

[88]  Ole A. Andreassen,et al.  Huntington's Disease of the Endocrine Pancreas: Insulin Deficiency and Diabetes Mellitus due to Impaired Insulin Gene Expression , 2002, Neurobiology of Disease.

[89]  Christopher A. Ross,et al.  Huntingtin Spheroids and Protofibrils as Precursors in Polyglutamine Fibrilization* , 2002, The Journal of Biological Chemistry.

[90]  Wolfgang Schmid,et al.  Disruption of CREB function in brain leads to neurodegeneration , 2002, Nature Genetics.

[91]  L. Ellerby,et al.  Calpain Activation in Huntington's Disease , 2002, The Journal of Neuroscience.

[92]  Dimitri Krainc,et al.  Sp1 and TAFII130 Transcriptional Activity Disrupted in Early Huntington's Disease , 2002, Science.

[93]  H. Lehrach,et al.  Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[94]  K. Lindenberg,et al.  Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. , 2002, Molecular cell.

[95]  L. Raymond,et al.  Increased Sensitivity to N-Methyl-D-Aspartate Receptor-Mediated Excitotoxicity in a Mouse Model of Huntington's Disease , 2002, Neuron.

[96]  Rainer Duden,et al.  Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. , 2002, Human molecular genetics.

[97]  James R. Burke,et al.  Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines , 2002, Nature Neuroscience.

[98]  I. Kanazawa,et al.  Interaction between Mutant Ataxin-1 and PQBP-1 Affects Transcription and Cell Death , 2002, Neuron.

[99]  S. Hersch,et al.  Therapeutic Effects of Cystamine in a Murine Model of Huntington's Disease , 2002, The Journal of Neuroscience.

[100]  S. Brenner,et al.  Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine , 2002, Nature Medicine.

[101]  M. MacDonald,et al.  Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice. , 2002, Human molecular genetics.

[102]  Suzanne Imbriglio.  Environmental Enrichment Slows Disease Progression in R6/2 Huntingtonʼs Disease Mice. , 2002 .

[103]  R. Ferrante,et al.  Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington's disease , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[104]  Rajiv R. Ratan,et al.  Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[105]  M. Beal,et al.  Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington's disease , 2003, Journal of neurochemistry.

[106]  I. V. Kovtun,et al.  Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in Huntington's disease , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[107]  He Li,et al.  Mutant Huntingtin Causes Context-Dependent Neurodegeneration in Mice with Huntington's Disease , 2003, The Journal of Neuroscience.

[108]  M. Mattson,et al.  Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[109]  M. MacDonald,et al.  Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. , 2003, Human molecular genetics.

[110]  Robert M Friedlander,et al.  Apoptosis and caspases in neurodegenerative diseases. , 2003, The New England journal of medicine.

[111]  G. Johnson,et al.  Cystamine Inhibits Caspase Activity , 2003, The Journal of Biological Chemistry.

[112]  Junying Yuan,et al.  Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders , 2003, Nature.

[113]  G. Bates,et al.  Minocycline and doxycycline are not beneficial in a model of Huntington's disease , 2003, Annals of neurology.

[114]  Dosage effects of riluzole in Huntington’s disease , 2003, Neurology.

[115]  Leslie Michels Thompson,et al.  A Rapid Cellular FRET Assay of Polyglutamine Aggregation Identifies a Novel Inhibitor , 2003, Neuron.

[116]  B. Hyman,et al.  Alzheimer disease's double-edged vaccine , 2003, Nature Medicine.

[117]  Leslie M Thompson,et al.  Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[118]  Cathryn M Lewis,et al.  Standardization and statistical approaches to therapeutic trials in the R6/2 mouse , 2003, Brain Research Bulletin.

[119]  Richard G. Brusch,et al.  Disruption of Axonal Transport by Loss of Huntingtin or Expression of Pathogenic PolyQ Proteins in Drosophila , 2003, Neuron.

[120]  D. Chuang,et al.  Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington’s disease , 2003, Molecular and Cellular Neuroscience.

[121]  C. Ross,et al.  Transglutaminase Cross‐Links in Intranuclear Inclusions in Huntington Disease , 2003, Journal of neuropathology and experimental neurology.

[122]  Alessandro Filla,et al.  DNA damage induced by polyglutamine-expanded proteins. , 2003, Human molecular genetics.

[123]  H. Reichmann,et al.  Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential , 2003, BioFactors.

[124]  S. Hersch,et al.  Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice , 2003, Journal of neurochemistry.

[125]  S. Krajewski,et al.  Calpain Is a Major Cell Death Effector in Selective Striatal Degeneration Induced In Vivo by 3-Nitropropionate: Implications for Huntington's Disease , 2003, The Journal of Neuroscience.

[126]  Ruth Luthi-Carter,et al.  Histone Deacetylase Inhibition by Sodium Butyrate Chemotherapy Ameliorates the Neurodegenerative Phenotype in Huntington's Disease Mice , 2003, The Journal of Neuroscience.

[127]  M. MacDonald,et al.  Plans for HDBase—a research community website for Huntington's Disease , 2003, Clinical Neuroscience Research.

[128]  E. Simpson,et al.  Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. , 2003, Human molecular genetics.

[129]  A. Messer,et al.  DNA vaccination against mutant huntingtin ameliorates the HDR6/2 diabetic phenotype. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[130]  S. Lorenzl,et al.  Minocycline enhances MPTP toxicity to dopaminergic neurons , 2003, Journal of neuroscience research.

[131]  R. Ferrante,et al.  Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[132]  Ewa Witort,et al.  Coenzyme Q10 Prevents Apoptosis by Inhibiting Mitochondrial Depolarization Independently of Its Free Radical Scavenging Property* , 2003, Journal of Biological Chemistry.

[133]  Scott T. Brady,et al.  Neuropathogenic Forms of Huntingtin and Androgen Receptor Inhibit Fast Axonal Transport , 2003, Neuron.

[134]  Thomas Walther,et al.  Transgenic rat model of Huntington's disease. , 2003, Human molecular genetics.

[135]  James E Bear,et al.  A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[136]  Weizhao Zhao,et al.  Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia , 2003, Annals of neurology.

[137]  N. Wood,et al.  Chronic lithium chloride treatment has variable effects on motor behaviour and survival of mice transgenic for the Huntington’s disease mutation , 2003, Brain Research Bulletin.

[138]  M. Beal,et al.  Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis , 2003, Journal of neurochemistry.

[139]  K. Hoyt,et al.  CRE-Mediated Transcription Is Increased in Huntington's Disease Transgenic Mice , 2004, The Journal of Neuroscience.

[140]  T. Caserta,et al.  Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties , 2003, Apoptosis.

[141]  Vincent Frouin,et al.  Striatal neural grafting improves cortical metabolism in Huntington's disease patients. , 2004, Brain : a journal of neurology.

[142]  C. Blakemore,et al.  Environmental Enrichment Rescues Protein Deficits in a Mouse Model of Huntington's Disease, Indicating a Possible Disease Mechanism , 2004, The Journal of Neuroscience.

[143]  N. Nukina,et al.  Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease , 2004, Nature Medicine.