Dimitri Krainc

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway
    Hyunkyung Jeong
    Department of Neurology, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, Massachusetts, USA
    Nat Med 18:159-65. 2012
  2. ncbi request reprint Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration
    Libin Cui
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129 USA
    Cell 127:59-69. 2006
  3. pmc Acetylation targets mutant huntingtin to autophagosomes for degradation
    Hyunkyung Jeong
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129, USA
    Cell 137:60-72. 2009
  4. ncbi request reprint Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease
    Alice S Chen-Plotkin
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital B114 2000, 114 16th Street, Charlestown, MA 02129 4404, USA
    Neurobiol Dis 22:233-41. 2006
  5. ncbi request reprint Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease
    Anthone W Dunah
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Center for Aging, Genetics and Neurodegeneration, Charlestown, MA 02129, USA
    Science 296:2238-43. 2002
  6. ncbi request reprint Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain
    Ruth Luthi-Carter
    Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital, Charlestown, MA 02129 4404, USA
    Hum Mol Genet 11:1911-26. 2002
  7. pmc Identification of novel ATP13A2 interactors and their role in α-synuclein misfolding and toxicity
    Marija Usenovic
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA
    Hum Mol Genet 21:3785-94. 2012
  8. doi request reprint Clearance of mutant proteins as a therapeutic target in neurodegenerative diseases
    Dimitri Krainc
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114 16th St, Room 2007, Charlestown, MA 02129, USA
    Arch Neurol 67:388-92. 2010
  9. pmc Deficiency of ATP13A2 leads to lysosomal dysfunction, α-synuclein accumulation, and neurotoxicity
    Marija Usenovic
    Department of Neurology, Harvard Medical School, Boston, MA, USA
    J Neurosci 32:4240-6. 2012
  10. pmc Lysosomal dysfunction in neurodegeneration: the role of ATP13A2/PARK9
    Marija Usenovic
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA
    Autophagy 8:987-8. 2012

Collaborators

Detail Information

Publications18

  1. pmc Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway
    Hyunkyung Jeong
    Department of Neurology, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, Massachusetts, USA
    Nat Med 18:159-65. 2012
    ..These studies suggest a key role for Sirt1 in transcriptional networks in both the normal and Huntington's disease brain and offer an opportunity for therapeutic development...
  2. ncbi request reprint Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration
    Libin Cui
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129 USA
    Cell 127:59-69. 2006
    ..These studies suggest a key role for PGC-1alpha in the control of energy metabolism in the early stages of HD pathogenesis...
  3. pmc Acetylation targets mutant huntingtin to autophagosomes for degradation
    Hyunkyung Jeong
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129, USA
    Cell 137:60-72. 2009
    ..These studies identify acetylation as a mechanism for removing accumulated protein in HD, and more broadly for actively targeting proteins for degradation by autophagy...
  4. ncbi request reprint Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease
    Alice S Chen-Plotkin
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital B114 2000, 114 16th Street, Charlestown, MA 02129 4404, USA
    Neurobiol Dis 22:233-41. 2006
    ..Moreover, the altered binding seen with Sp1 is not found with another transcription factor, NF-Y. These findings suggest that mutant huntingtin dissociates Sp1 from target promoters, inhibiting transcription of specific genes...
  5. ncbi request reprint Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease
    Anthone W Dunah
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Center for Aging, Genetics and Neurodegeneration, Charlestown, MA 02129, USA
    Science 296:2238-43. 2002
    ..Understanding these early molecular events in HD may provide an opportunity to interfere with the effects of mutant huntingtin before the development of disease symptoms...
  6. ncbi request reprint Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain
    Ruth Luthi-Carter
    Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital, Charlestown, MA 02129 4404, USA
    Hum Mol Genet 11:1911-26. 2002
    ..The complete dataset is available at www.neumetrix.info...
  7. pmc Identification of novel ATP13A2 interactors and their role in α-synuclein misfolding and toxicity
    Marija Usenovic
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA
    Hum Mol Genet 21:3785-94. 2012
    ..These results implicate ATP13A2 in vesicular trafficking and provide a platform for further studies of ATP13A2 in neurodegeneration...
  8. doi request reprint Clearance of mutant proteins as a therapeutic target in neurodegenerative diseases
    Dimitri Krainc
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114 16th St, Room 2007, Charlestown, MA 02129, USA
    Arch Neurol 67:388-92. 2010
    ....
  9. pmc Deficiency of ATP13A2 leads to lysosomal dysfunction, α-synuclein accumulation, and neurotoxicity
    Marija Usenovic
    Department of Neurology, Harvard Medical School, Boston, MA, USA
    J Neurosci 32:4240-6. 2012
    ..Our findings implicate lysosomal dysfunction in the pathogenesis of Kufor-Rakeb syndrome and suggest that upregulation of lysosomal function and downregulation of α-synuclein represent important therapeutic strategies for this disorder...
  10. pmc Lysosomal dysfunction in neurodegeneration: the role of ATP13A2/PARK9
    Marija Usenovic
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA
    Autophagy 8:987-8. 2012
    ....
  11. ncbi request reprint Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
    Jiandie Lin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 119:121-35. 2004
    ..These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis...
  12. pmc Peroxisome-proliferator-activated receptor gamma coactivator 1 α contributes to dysmyelination in experimental models of Huntington's disease
    Zhongmin Xiang
    MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 31:9544-53. 2011
    ..Together, these data suggest that PGC1α plays a role in postnatal myelination and that deficient PGC1α activity in oligodendrocytes may contribute to abnormal myelination in HD...
  13. pmc Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome: implications for normal aging and age-dependent neurodegenerative disorders
    John J Graziotto
    Department of Neurology, Massachusetts General Hospital, MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, MA, USA
    Autophagy 8:147-51. 2012
    ..In addition to its role in HGPS and normal aging, we discuss the potential of rapamycin for the treatment of age-dependent neurodegenerative diseases...
  14. pmc Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies
    Joseph R Mazzulli
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA
    Cell 146:37-52. 2011
    ..Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies...
  15. pmc Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells
    Philip Seibler
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Mass General Institute for Neurodegenerative Disease, Charlestown, Massachusetts 02129, USA
    J Neurosci 31:5970-6. 2011
    ..These neurons exhibit distinct phenotypes that should be amenable to further mechanistic studies in this relevant biological context...
  16. pmc Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors
    Kimberly B Kegel
    Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Mol Neurodegener 5:58. 2010
    ..abstract:..
  17. ncbi request reprint Sodium phenylbutyrate in Huntington's disease: a dose-finding study
    Penelope Hogarth
    Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239 3098, USA
    Mov Disord 22:1962-4. 2007
    ..We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD...
  18. pmc Neuronal activity and secreted amyloid β lead to altered amyloid β precursor protein and presenilin 1 interactions
    Xuejing Li
    Neurobiology of Alzheimer s Disease Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Neurobiol Dis 50:127-34. 2013
    ..Thus, under normal physiological conditions Aβ may impact its own production by modifying γ-secretase cleavage of APP. Disruption of this negative modulation may cause Aβ overproduction leading to neurotoxicity...

Research Grants12

  1. Protein Acetylation and Selective Autophagy
    Dimitri Krainc; Fiscal Year: 2010
    ..We propose to develop strategies to selectively activate cellular degradation machinery to improve clearance of mutant huntingtin and identify novel therapeutic targets for the treatment of HD and related neurodegenerative disorders. ..
  2. Transcriptional Regulation of PGC-1 in Huntington's Disease
    Dimitri Krainc; Fiscal Year: 2010
    ....
  3. Transcriptional Regulation of PGC-1 in Huntington's Disease
    Dimitri Krainc; Fiscal Year: 2009
    ....
  4. Protein Acetylation and Selective Autophagy
    Dimitri Krainc; Fiscal Year: 2010
    ..We propose to develop strategies to selectively activate cellular degradation machinery to improve clearance of mutant huntingtin and identify novel therapeutic targets for the treatment of HD and related neurodegenerative disorders. ..
  5. Transcriptional Regulation of PGC-1 in Huntington's Disease
    Dimitri Krainc; Fiscal Year: 2009
    ....
  6. Transcriptional Regulation of PGC-1 in Huntington's Disease
    Dimitri Krainc; Fiscal Year: 2010
    ....
  7. Transcriptional Regulation of PGC-1 in Huntington's Disease
    Dimitri Krainc; Fiscal Year: 2009
    ....
  8. MECHANISMS OF TRANSCRIPTIONAL REPRESSION IN HUNTINGTON'S DISEASE
    Dimitri Krainc; Fiscal Year: 2007
    ..Completion of these aims should reveal new insights into general mechanisms of polyglutamine-induced neurodegeneration and lead to identification of new molecular targets for therapies in HD. ..
  9. MECHANISMS OF TRANSCRIPTIONAL REPRESSION IN HUNTINGTON'S
    Dimitri Krainc; Fiscal Year: 2006
    ..Completion of these aims should reveal new insights into general mechanisms of polyglutamine-induced neurodegeneration and lead to identification of new molecular targets for therapies in HD. ..
  10. EFFECTS OF HUNTINGTON ON GENE TRANSCRIPTION
    Dimitri Krainc; Fiscal Year: 2004
    ..Identification of such molecular mechanisms in the pathogenesis of polyglutamine disorders may help identify possible targets for future therapeutics. ..