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Genomes and Genes | Kimberly B KegelSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcriptionKimberly 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...- Huntingtin associates with acidic phospholipids at the plasma membraneKimberly 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... 
Mutant huntingtin impairs vesicle formation from recycling endosomes by interfering with Rab11 activityXueyi 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...
Aberrant Rab11-dependent trafficking of the neuronal glutamate transporter EAAC1 causes oxidative stress and cell death in Huntington's diseaseXueyi 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...- Reagents that block neuronal death from Huntington's disease also curb oxidative stressAntonio 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... - Polyglutamine expansion in huntingtin alters its interaction with phospholipidsKimberly 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... - Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's diseaseAntonio 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... - Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interactionZheng 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... - Lysosomal proteases are involved in generation of N-terminal huntingtin fragmentsYun 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... - Native mutant huntingtin in human brain: evidence for prevalence of full-length monomerEllen 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... - Disruption of Rab11 activity in a knock-in mouse model of Huntington's diseaseXueyi 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... - A function of huntingtin in guanine nucleotide exchange on Rab11Xueyi 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... - Multiple phenotypes in Huntington disease mouse neural stem cellsJames 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... - Polyglutamine expansion in huntingtin increases its insertion into lipid bilayersKimberly 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... - Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease miceXueyi 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... - Elevated NADPH oxidase activity contributes to oxidative stress and cell death in Huntington's diseaseAntonio 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... - Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitorsKimberly B Kegel
Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
Mol Neurodegener 5:58. 2010..abstract:.. - Autophagy regulates the processing of amino terminal huntingtin fragmentsZheng-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...