Access the full text.
Sign up today, get DeepDyve free for 14 days.
J. Vonsattel, R. Myers, Thomas Stevens, R. Ferrante, E. Bird, E. Richardson (1985)
Neuropathological Classification of Huntington's DiseaseJournal of Neuropathology and Experimental Neurology, 44
C. Soneson, Magnus Fontes, Yongxia Zhou, V. Denisov, Jane Paulsen, D. Kirik, Å. Petersén (2010)
Early changes in the hypothalamic region in prodromal Huntington disease revealed by MRI analysisNeurobiology of Disease, 40
Z. Xiang, M. Valenza, Libin Cui, V. Leoni, H. Jeong, E. Brilli, Jiangyang Zhang, Qi Peng, W. Duan, S. Reeves, E. Cattaneo, D. Krainc (2011)
Peroxisome-Proliferator-Activated Receptor Gamma Coactivator 1 α Contributes to Dysmyelination in Experimental Models of Huntington's DiseaseThe Journal of Neuroscience, 31
M. Mańczak, P. Mao, Markus Calkins, A. Cornea, A. Reddy, Michael Murphy, Hazel Szeto, Byung Park, P. Reddy, P. Reddy (2010)
Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer's disease neurons.Journal of Alzheimer's disease : JAD, 20 Suppl 2
J. Vonsattel (2007)
Huntington disease models and human neuropathology: similarities and differencesActa Neuropathologica, 115
M. Calkins, P. Reddy, P. Reddy (2011)
Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer's disease neurons.Biochimica et biophysica acta, 1812 4
V. André, C. Cepeda, Yvette Fisher, M. Huynh, Nora Bardakjian, Sumedha Singh, X. Yang, M. Levine (2011)
Differential Electrophysiological Changes in Striatal Output Neurons in Huntington's DiseaseThe Journal of Neuroscience, 31
M. Difiglia, E. Sapp, K. Chase, S. Davies, G. Bates, J. Vonsattel, N. Aronin (1997)
Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.Science, 277 5334
Anne Strehlow, Jun Li, R. Myers (2007)
Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space.Human molecular genetics, 16 4
Joseph Martin (1984)
Huntington's diseaseNeurology, 34
J. St-Pierre, S. Drori, M. Uldry, Jessica Silvaggi, James Rhee, S. Jäger, C. Handschin, Kangni Zheng, Jiandie Lin, Wenli Yang, D. Simon, R. Bachoo, B. Spiegelman (2006)
Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional CoactivatorsCell, 127
E. Mailloux (1989)
Engineering information systems, 24
G. Gilbert (2008)
Weight loss in Huntington disease increases with higher CAG repeat numberNeurology, 71
U. Shirendeb, A. Reddy, M. Mańczak, M. Calkins, P. Mao, D. Tagle, P. Reddy (2011)
Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington's disease: implications for selective neuronal damage.Human molecular genetics, 20 7
M. Politis, N. Pavese, Y. Tai, S. Tabrizi, R. Barker, P. Piccini (2008)
Hypothalamic involvement in Huntington's disease: an in vivo PET study.Brain : a journal of neurology, 131 Pt 11
K. Kegel, E. Sapp, Jennifer Yoder, B. Cuiffo, Lindsay Sobin, Yun Kim, Zheng-Hong Qin, M. Hayden, N. Aronin, D. Scott, G. Isenberg, W. Goldmann, M. Difiglia (2005)
Huntingtin Associates with Acidic Phospholipids at the Plasma Membrane*Journal of Biological Chemistry, 280
Glenda Halliday, D. McRitchie, V. Macdonald, Kay Double, Ronald Trent, Elizabeth McCusker (1998)
Regional Specificity of Brain Atrophy in Huntington's DiseaseExperimental Neurology, 154
P. Gill, W. Murray, M. Saunders, M. Wright (1983)
Computing Forward-Difference Intervals for Numerical OptimizationSiam Journal on Scientific and Statistical Computing, 4
Libin Cui, Hyunkyung Jeong, F. Borovečki, Christopher Parkhurst, N. Tanese, D. Krainc (2006)
Transcriptional Repression of PGC-1α by Mutant Huntingtin Leads to Mitochondrial Dysfunction and NeurodegenerationCell, 127
Ai Yamamoto, J. Lucas, R. Hen (2000)
Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's DiseaseCell, 101
Jay Spampanato, X. Gu, X. Yang, Istvan Mody (2008)
Progressive synaptic pathology of motor cortical neurons in a BAC transgenic mouse model of Huntington's diseaseNeuroscience, 157
N. Aziz (2009)
Weight loss in Huntington’s disease increases with higher CAG repeat number
V. Wheeler, W. Auerbach, Jacqueline White, J. Srinidhi, A. Auerbach, Angela Ryan, M. Duyao, V. Vrbanac, Meredith Weaver, J. Gusella, A. Joyner, M. MacDonald (1999)
Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse.Human molecular genetics, 8 1
L. Menalled, B. El-Khodor, Monica Patry, M. Suárez-Fariñas, Samantha Orenstein, Benjamin Zahasky, Christina Leahy, V. Wheeler, X. Yang, M. MacDonald, A. Morton, G. Bates, Janet Leeds, L. Park, D. Howland, E. Signer, A. Tobin, D. Brunner (2009)
Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse modelsNeurobiology of Disease, 35
S. Ms, A. Falek (2008)
Huntington's DiseaseLoss, grief & care
Junko Wakabayashi, Zhongyang Zhang, N. Wakabayashi, Y. Tamura, M. Fukaya, T. Kensler, M. Iijima, H. Sesaki (2009)
The dynamin-related GTPase Drp1 is required for embryonic and brain development in miceThe Journal of Cell Biology, 186
R. Atwal, Jianrun Xia, Deborah Pinchev, Jillian Taylor, R. Epand, R. Truant (2007)
Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity.Human molecular genetics, 16 21
M. Levine, G. Klapstein, Ahrin Koppel, E. Gruen, C. Cepeda, M. Vargas, E. Jokel, E. Carpenter, H. Zanjani, R. Hurst, A. Efstratiadis, S. Zeitlin, M. Chesselet (1999)
Enhanced sensitivity to N‐methyl‐D‐aspartate receptor activation in transgenic and knockin mouse models of Huntington's diseaseJournal of Neuroscience Research, 58
M. Gray, Dyna Shirasaki, C. Cepeda, V. André, B. Wilburn, Xiao-Hong Lu, Jifang Tao, I. Yamazaki, Shihua Li, Y. Sun, Xiao-Jiang Li, M. Levine, X. Yang (2008)
Full-Length Human Mutant Huntingtin with a Stable Polyglutamine Repeat Can Elicit Progressive and Selective Neuropathogenesis in BACHD MiceThe Journal of Neuroscience, 28
X. Gu, E. Greiner, R. Mishra, Ravindra Kodali, A. Osmand, S. Finkbeiner, J. Steffan, Leslie Thompson, R. Wetzel, X. Yang (2009)
Serines 13 and 16 Are Critical Determinants of Full-Length Human Mutant Huntingtin Induced Disease Pathogenesis in HD MiceNeuron, 64
Hongmin Wang, Precious Lim, M. Karbowski, M. Monteiro (2009)
Effects of overexpression of huntingtin proteins on mitochondrial integrity.Human molecular genetics, 18 4
Wenjun Song, Jin Chen, A. Petrilli, G. Liot, E. Klinglmayr, Yue Zhou, Patrick Poquiz, Jonathan Tjong, M. Pouladi, M. Hayden, E. Masliah, Mark Ellisman, I. Rouiller, R. Schwarzenbacher, B. Bossy, G. Perkins, E. Bossy‐Wetzel (2011)
MUTANT HUNTINGTIN BINDS THE MITOCHONDRIAL FISSION GTPASE DRP1 AND INCREASES ITS ENZYMATIC ACTIVTYNature medicine, 17
M. Calkins, P. Reddy (2011)
Assessment of newly synthesized mitochondrial DNA using BrdU labeling in primary neurons from Alzheimer's disease mice: Implications for impaired mitochondrial biogenesis and synaptic damage.Biochimica et biophysica acta, 1812 9
S. Davies, M. Turmaine, Barbara Cozens, M. Difiglia, A. Sharp, C. Ross, E. Scherzinger, E. Wanker, L. Mangiarini, G. Bates (1997)
Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD MutationCell, 90
M. Mańczak, M. Calkins, P. Reddy (2011)
Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage.Human molecular genetics, 20 13
Joanne Hamilton, T. Wolfson, G. Peavy, Mark Jacobson, J. Corey-Bloom (2004)
Rate and correlates of weight change in Huntington’s disease*Journal of Neurology, Neurosurgery & Psychiatry, 75
S. Hult, R. Soylu, T. Björklund, B. Belgardt, J. Mauer, J. Brüning, D. Kirik, Å. Petersén (2011)
Mutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits.Cell metabolism, 13 4
P. Weydt, Victor Pineda, A. Torrence, R. Libby, Terrence Satterfield, E. Lazarowski, M. Gilbert, G. Morton, T. Bammler, A. Strand, Libin Cui, R. Beyer, Courtney Easley, ANNETTE Smith, D. Krainc, S. Luquet, I. Sweet, M. Schwartz, A. Spada (2006)
Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration.Cell metabolism, 4 5
P. Reddy, Maya Williams, V. Charles, L. Garrett, Lisa Pike-Buchanan, W. Whetsell, G. Miller, D. Tagle (1998)
Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNANature Genetics, 20
P. Reddy, T. Reddy, M. Mańczak, M. Calkins, U. Shirendeb, P. Mao (2011)
Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseasesBrain Research Reviews, 67
M. Pouladi, Y. Xie, N. Skotte, Dagmar Ehrnhoefer, R. Graham, Jeong Kim, N. Bissada, X. Yang, P. Paganetti, R. Friedlander, B. Leavitt, M. Hayden (2010)
Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression.Human molecular genetics, 19 8
D. Chan (2006)
Mitochondrial fusion and fission in mammals.Annual review of cell and developmental biology, 22
J. Phan, M. Hickey, Peixiang Zhang, M. Chesselet, K. Reue (2009)
Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models.Human molecular genetics, 18 6
A. Orr, Shihua Li, Chuan-en Wang, He Li, Jianjun Wang, Juan Rong, Xingshun Xu, P. Mastroberardino, J. Greenamyre, Xiao-Jiang Li (2008)
N-Terminal Mutant Huntingtin Associates with Mitochondria and Impairs Mitochondrial TraffickingThe Journal of Neuroscience, 28
A. Montoya, B. Price, Matthew Menear, M. Lepage (2006)
Brain imaging and cognitive dysfunctions in Huntington's disease.Journal of psychiatry & neuroscience : JPN, 31 1
Gabriele Schilling, M. Becher, A. Sharp, H. Jinnah, Kui Duan, J. Kotzuk, H. Slunt, T. Ratovitski, J. Cooper, N. Jenkins, N. Copeland, D. Price, C. Ross, D. Borchelt (1999)
Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin.Human molecular genetics, 8 3
A. Panov, C. Gutekunst, B. Leavitt, M. Hayden, J. Burke, W. Strittmatter, J. Greenamyre (2002)
Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutaminesNature Neuroscience, 5
Y. Kageyama, Zhongyang Zhang, H. Sesaki (2011)
Mitochondrial division: molecular machinery and physiological functions.Current opinion in cell biology, 23 4
P. Reddy, P. Mao, M. Mańczak (2009)
Mitochondrial structural and functional dynamics in Huntington's diseaseBrain Research Reviews, 61
J. Neurosci. Res
M. Calkins, M. Mańczak, P. Mao, U. Shirendeb, P. Reddy (2011)
Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease.Human molecular genetics, 20 23
A. Southwell, J. Ko, P. Patterson (2009)
Intrabody Gene Therapy Ameliorates Motor, Cognitive, and Neuropathological Symptoms in Multiple Mouse Models of Huntington's DiseaseThe Journal of Neuroscience, 29
R. Truant, R. Atwal, Anjee Burtnik (2006)
Hypothesis: Huntingtin may function in membrane association and vesicular trafficking.Biochemistry and cell biology = Biochimie et biologie cellulaire, 84 6
P. Moreira, Xiongwei Zhu, Xinglong Wang, Hyoung-Gon Lee, A. Nunomura, R. Petersen, George Perry, Mark Smith (2010)
Mitochondria: a therapeutic target in neurodegeneration.Biochimica et biophysica acta, 1802 1
Yeun Choo, G. Johnson, M. MacDonald, P. Detloff, M. Lesort (2004)
Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release.Human molecular genetics, 13 14
Y. Trottier, Y. Lutz, G. Stevanin, G. Imbert, D. Devys, G. Cancel, F. Saudou, C. Weber, Gilles David, L. Tora, Y. Agid, A. Brice, J. Mandel (1995)
Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxiasNature, 378
R. Chaturvedi, P. Adhihetty, S. Shukla, Thomas Hennessy, N. Calingasan, Lichuan Yang, A. Starkov, M. Kiaei, M. Cannella, J. Sassone, A. Ciammola, F. Squitieri, M. Beal (2009)
Impaired PGC-1alpha function in muscle in Huntington's disease.Human molecular genetics, 18 16
Naotada Ishihara, M. Nomura, A. Jofuku, H. Kato, Satoshi Suzuki, K. Masuda, H. Otera, Yae Nakanishi, I. Nonaka, Yu-ichi Goto, Naoko Taguchi, H. Morinaga, Maki Maeda, R. Takayanagi, S. Yokota, K. Mihara (2009)
Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in miceNature Cell Biology, 11
K. Kegel, A. Meloni, Y. Yi, Yun Kim, E. Doyle, B. Cuiffo, E. Sapp, Yumei Wang, Zheng-Hong Qin, J. Chen, J. Nevins, N. Aronin, M. Difiglia (2002)
Huntingtin Is Present in the Nucleus, Interacts with the Transcriptional Corepressor C-terminal Binding Protein, and Represses Transcription*The Journal of Biological Chemistry, 277
S. Kirkwood, J. Su, P. Conneally, T. Foroud (2001)
Progression of symptoms in the early and middle stages of Huntington disease.Archives of neurology, 58 2
Jinho Kim, Jinho Kim, Jennifer Moody, Jennifer Moody, C. Edgerly, Olivia Bordiuk, K. Cormier, Karen Smith, Karen Smith, M. Beal, R. Ferrante, R. Ferrante (2010)
Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease.Human molecular genetics, 19 20
R. Gutala, P. Reddy (2004)
The use of real-time PCR analysis in a gene expression study of Alzheimer’s disease post-mortem brainsJournal of Neuroscience Methods, 132
D. Lewis (1991)
Matrix theory
C. Ross, S. Tabrizi (2011)
Huntington's disease: from molecular pathogenesis to clinical treatmentThe Lancet Neurology, 10
M. MacDonald, C. Ambrose, M. Duyao, R. Myers, Carol Lin, L. Srinidhi, G. Barnes, Sherryl Taylor, M. James, Nicolet Groot, Heather Macfarlane, B. Jenkins, M. Anderson, N. Wexler, J. Gusella, G. Bates, S. Baxendale, H. Hummerich, S. Kirby, M. North, S. Youngman, R. Mott, G. Zehetner, Z. Sedlacek, A. Poustka, A. Frischauf, H. Lehrach, A. Buckler, D. Church, L. Doucette-Stamm, M. O’Donovan, Laura Riba-Ramírez, Manish Shah, V. Stanton, S. Strobel, K. Draths, Jennifer Wales, P. Dervan, D. Housman, M. Altherr, R. Shiang, L. Thompson, T. Fielder, J. Wasmuth, D. Tagle, J. Valdes, Lon Elmer, M. Allard, L. Castilla, M. Swaroop, K. Blanchard, F. Collins, R. Snell, T. Holloway, Kathleen Gillespie, N. Datson, D. Shaw, P. Harper (1993)
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomesCell, 72
L. Mangiarini, K. Sathasivam, M. Seller, Barbara Cozens, Alex Harper, C. Hetherington, Martin Lawton, Y. Trottier, H. Lehrach, S. Davies, G. Bates (1996)
Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic MiceCell, 87
T. Kudo, A. Schroeder, D. Loh, D. Kuljis, M. Jordan, K. Roos, C. Colwell (2011)
Dysfunctions in circadian behavior and physiology in mouse models of Huntington's diseaseExperimental Neurology, 228
E. Spargo, I. Everall, P. Lantos (1993)
Neuronal loss in the hippocampus in Huntington's disease: a comparison with HIV infection.Journal of Neurology, Neurosurgery & Psychiatry, 56
J. Hodgson, N. Agopyan, C. Gutekunst, B. Leavitt, F. LePiane, R. Singaraja, Desmond Smith, N. Bissada, K. McCutcheon, J. Nasir, L. Jamot, Xiao-Jiang Li, M. Stevens, Erica Rosemond, J. Roder, A. Phillips, E. Rubin, S. Hersch, M. Hayden (1999)
A YAC Mouse Model for Huntington’s Disease with Full-Length Mutant Huntingtin, Cytoplasmic Toxicity, and Selective Striatal NeurodegenerationNeuron, 23
The purpose of this study was to investigate the link between mutant huntingtin (Htt) and neuronal damage in relation to mitochondria in Huntington's disease (HD). In an earlier study, we determined the relationship between mutant Htt and mitochondrial dynamics/synaptic viability in HD patients. We found mitochondrial loss, abnormal mitochondrial dynamics and mutant Htt association with mitochondria in HD patients. In the current study, we sought to expand on our previous findings and further elucidate the relationship between mutant Htt and mitochondrial and synaptic deficiencies. We hypothesized that mutant Htt, in association with mitochondria, alters mitochondrial dynamics, leading to mitochondrial fragmentation and defective axonal transport of mitochondria in HD neurons. In this study, using postmortem HD brains and primary neurons from transgenic BACHD mice, we identified mutant Htt interaction with the mitochondrial protein Drp1 and factors that cause abnormal mitochondrial dynamics, including GTPase Drp1 enzymatic activity. Further, using primary neurons from BACHD mice, for the first time, we studied axonal transport of mitochondria and synaptic degeneration. We also investigated the effect of mutant Htt aggregates and oligomers in synaptic and mitochondrial deficiencies in postmortem HD brains and primary neurons from BACHD mice. We found that mutant Htt interacts with Drp1, elevates GTPase Drp1 enzymatic activity, increases abnormal mitochondrial dynamics and results in defective anterograde mitochondrial movement and synaptic deficiencies. These observations support our hypothesis and provide data that can be utilized to develop therapeutic targets that are capable of inhibiting mutant Htt interaction with Drp1, decreasing mitochondrial fragmentation, enhancing axonal transport of mitochondria and protecting synapses from toxic insults caused by mutant Htt.
Human Molecular Genetics – Oxford University Press
Published: Jan 15, 2012
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.