Kimberly B Kegel

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription
    Kimberly B Kegel
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    J Biol Chem 277:7466-76. 2002
  2. ncbi request reprint Huntingtin associates with acidic phospholipids at the plasma membrane
    Kimberly B Kegel
    Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 280:36464-73. 2005
  3. pmc Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activity
    Xueyi Li
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Mol Cell Biol 29:6106-16. 2009
  4. pmc Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's disease
    Xueyi Li
    Cellular Neurobiology Laboratory and Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 30:4552-61. 2010
  5. doi request reprint Reagents that block neuronal death from Huntington's disease also curb oxidative stress
    Antonio Valencia
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
    Neuroreport 23:10-5. 2012
  6. ncbi request reprint Polyglutamine expansion in huntingtin alters its interaction with phospholipids
    Kimberly B Kegel
    Laboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, 11416th Street, Room 2150, Charlestown, MA 02129, USA
    J Neurochem 110:1585-97. 2009
  7. doi request reprint Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's disease
    Antonio Valencia
    Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    J Neurosci Res 88:179-90. 2010
  8. pmc Elevated NADPH oxidase activity contributes to oxidative stress and cell death in Huntington's disease
    Antonio Valencia
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA
    Hum Mol Genet 22:1112-31. 2013
  9. ncbi request reprint Lysosomal proteases are involved in generation of N-terminal huntingtin fragments
    Yun J Kim
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Neurobiol Dis 22:346-56. 2006
  10. ncbi request reprint Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction
    Zheng Hong Qin
    Laboratory of Cellular Neurobiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 24:269-81. 2004

Collaborators

Detail Information

Publications19

  1. ncbi request reprint Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription
    Kimberly B Kegel
    Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
    J Biol Chem 277:7466-76. 2002
    ..Proteolysis of mutant huntingtin may alter nuclear functions by disrupting protein complexes and inappropriately repressing transcription in HD...
  2. ncbi request reprint Huntingtin associates with acidic phospholipids at the plasma membrane
    Kimberly B Kegel
    Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 280:36464-73. 2005
    ..Our data support a new model in which huntingtin directly binds membranes through electrostatic interactions with acidic phospholipids...
  3. pmc Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activity
    Xueyi Li
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Mol Cell Biol 29:6106-16. 2009
    ..We propose a novel mechanism for cellular dysfunction by the HD mutation arising from the inhibition of Rab11 activity and a deficit in vesicle formation at recycling endosomes...
  4. pmc Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's disease
    Xueyi Li
    Cellular Neurobiology Laboratory and Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 30:4552-61. 2010
    ..Our data support a novel mechanism for oxidative stress in HD: Rab11 dysfunction slows trafficking of EAAC1 to the cell surface and impairs cysteine uptake, thereby leading to deficient synthesis of glutathione...
  5. doi request reprint Reagents that block neuronal death from Huntington's disease also curb oxidative stress
    Antonio Valencia
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
    Neuroreport 23:10-5. 2012
    ..These results suggest that reducing the levels of reactive oxygen species may be necessary to protect neurons with the Huntington's disease mutation from cell death...
  6. ncbi request reprint Polyglutamine expansion in huntingtin alters its interaction with phospholipids
    Kimberly B Kegel
    Laboratory of Cellular Neurobiology, Department of Neurology, Massachusetts General Hospital, 11416th Street, Room 2150, Charlestown, MA 02129, USA
    J Neurochem 110:1585-97. 2009
    ..These data suggest that huntingtin interacts with membranes through specific phospholipid associations and that mutant huntingtin may disrupt membrane trafficking and signaling at membranes...
  7. doi request reprint Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's disease
    Antonio Valencia
    Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    J Neurosci Res 88:179-90. 2010
    ..We speculate that accumulation of mutant huntingtin and glycogen synthase kinase 3-beta in lipid rafts of presymptomatic Huntington's disease mouse neurons contributes to neurodegeneration in Huntington's disease...
  8. pmc Elevated NADPH oxidase activity contributes to oxidative stress and cell death in Huntington's disease
    Antonio Valencia
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA
    Hum Mol Genet 22:1112-31. 2013
    ..These findings suggest that increased NOX2 activity at lipid rafts is an early and major source of oxidative stress and cell death in HD(140Q/140Q) neurons...
  9. ncbi request reprint Lysosomal proteases are involved in generation of N-terminal huntingtin fragments
    Yun J Kim
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Neurobiol Dis 22:346-56. 2006
    ..Findings implicate lysosomal proteases in formation of N-mhtt fragments and clearance of mhtt...
  10. ncbi request reprint Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction
    Zheng Hong Qin
    Laboratory of Cellular Neurobiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 24:269-81. 2004
    ..Results suggest that accumulation of a nonfibrillar form of mutant htt in the cytoplasm contributes to neuronal dysfunction by sequestering proteins involved in vesicle trafficking...
  11. pmc Native mutant huntingtin in human brain: evidence for prevalence of full-length monomer
    Ellen Sapp
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 287:13487-99. 2012
    ..Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer...
  12. pmc Disruption of Rab11 activity in a knock-in mouse model of Huntington's disease
    Xueyi Li
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Neurobiol Dis 36:374-83. 2009
    ..Partial rescue from glutamate-induced cell death occurred in HD neurons expressing dominant active Rab11. We propose a novel mechanism of HD pathogenesis arising from diminished Rab11 activity at recycling endosomes...
  13. doi request reprint A function of huntingtin in guanine nucleotide exchange on Rab11
    Xueyi Li
    Laboratory of Cellular Neurobiology and Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
    Neuroreport 19:1643-7. 2008
    ..These data suggest a role for huntingtin in a complex that activates Rab11...
  14. pmc Multiple phenotypes in Huntington disease mouse neural stem cells
    James J Ritch
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, United States
    Mol Cell Neurosci 50:70-81. 2012
    ..Our findings suggest that NS cells expressing endogenous mutant Htt will be useful for study of mechanisms of HD and drug discovery...
  15. doi request reprint Polyglutamine expansion in huntingtin increases its insertion into lipid bilayers
    Kimberly B Kegel
    Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 387:472-5. 2009
    ..We speculate that by inserting more into cell membranes, mutant huntingtin could increase disorder within the lipid bilayer and thereby disturb cellular membrane function...
  16. doi request reprint Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice
    Xueyi Li
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 421:727-30. 2012
    ..Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD(140Q/140Q) neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD...
  17. 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:..
  18. ncbi request reprint Assessment of Chloroquine Treatment for Modulating Autophagy Flux in Brain of WT and HD Mice
    Petr Vodicka
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
    J Huntingtons Dis 3:159-74. 2014
    ..Increasing mutant huntingtin (mHTT) clearance through the autophagy pathway may be a way to treat Huntington's disease (HD). Tools to manipulate and measure autophagy flux in brain in vivo are not well established...
  19. ncbi request reprint Autophagy regulates the processing of amino terminal huntingtin fragments
    Zheng Hong Qin
    Laboratory of Cellular Neurobiology, Masschusetts General Hospital and Harvard Medical School, Charlestown 02129, USA
    Hum Mol Genet 12:3231-44. 2003
    ..These results suggest that autophagy plays a critical role in the degradation of N-terminal htt. Altered processing of mutant htt by autophagy and cathepsin D may contribute to HD pathogenesis...