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Cleavage at the 586 amino acid caspase-6 site in mutant huntingtin influences caspase-6 activation in vivo.

Graham RK, Deng Y, Carroll J, Vaid K, Cowan C, Pouladi MA, Metzler M, Bissada N, Wang L, Faull RL, Gray M, Yang XW, Raymond LA, Hayden MR.

J Neurosci. 2010 Nov 10;30(45):15019-29. doi: 10.1523/JNEUROSCI.2071-10.2010.


Caspase-6-Resistant Mutant Huntingtin Does not Rescue the Toxic Effects of Caspase-Cleavable Mutant Huntingtin in vivo.

Graham RK, Deng Y, Pouladi MA, Vaid K, Ehrnhoefer D, Southwell AL, Bissada N, Franciosi S, Hayden MR.

J Huntingtons Dis. 2012;1(2):243-60. doi: 10.3233/JHD-120038.


Caspase-6 activity in a BACHD mouse modulates steady-state levels of mutant huntingtin protein but is not necessary for production of a 586 amino acid proteolytic fragment.

Gafni J, Papanikolaou T, Degiacomo F, Holcomb J, Chen S, Menalled L, Kudwa A, Fitzpatrick J, Miller S, Ramboz S, Tuunanen PI, Lehtimäki KK, Yang XW, Park L, Kwak S, Howland D, Park H, Ellerby LM.

J Neurosci. 2012 May 30;32(22):7454-65. doi: 10.1523/JNEUROSCI.6379-11.2012.


Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin.

Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, Lu G, Pearson J, Shehadeh J, Bertram L, Murphy Z, Warby SC, Doty CN, Roy S, Wellington CL, Leavitt BR, Raymond LA, Nicholson DW, Hayden MR.

Cell. 2006 Jun 16;125(6):1179-91.


Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease.

Hermel E, Gafni J, Propp SS, Leavitt BR, Wellington CL, Young JE, Hackam AS, Logvinova AV, Peel AL, Chen SF, Hook V, Singaraja R, Krajewski S, Goldsmith PC, Ellerby HM, Hayden MR, Bredesen DE, Ellerby LM.

Cell Death Differ. 2004 Apr;11(4):424-38.


Full length mutant huntingtin is required for altered Ca2+ signaling and apoptosis of striatal neurons in the YAC mouse model of Huntington's disease.

Zhang H, Li Q, Graham RK, Slow E, Hayden MR, Bezprozvanny I.

Neurobiol Dis. 2008 Jul;31(1):80-8. doi: 10.1016/j.nbd.2008.03.010. Epub 2008 Apr 16.


Genetic manipulations of mutant huntingtin in mice: new insights into Huntington's disease pathogenesis.

Lee CY, Cantle JP, Yang XW.

FEBS J. 2013 Sep;280(18):4382-94. doi: 10.1111/febs.12418. Epub 2013 Jul 31. Review.


Partial rescue of some features of Huntington Disease in the genetic absence of caspase-6 in YAC128 mice.

Wong BK, Ehrnhoefer DE, Graham RK, Martin DD, Ladha S, Uribe V, Stanek LM, Franciosi S, Qiu X, Deng Y, Kovalik V, Zhang W, Pouladi MA, Shihabuddin LS, Hayden MR.

Neurobiol Dis. 2015 Apr;76:24-36. doi: 10.1016/j.nbd.2014.12.030. Epub 2015 Jan 9.


Phosphorylation of huntingtin at Ser421 in YAC128 neurons is associated with protection of YAC128 neurons from NMDA-mediated excitotoxicity and is modulated by PP1 and PP2A.

Metzler M, Gan L, Mazarei G, Graham RK, Liu L, Bissada N, Lu G, Leavitt BR, Hayden MR.

J Neurosci. 2010 Oct 27;30(43):14318-29. doi: 10.1523/JNEUROSCI.1589-10.2010.


Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease.

Wellington CL, Ellerby LM, Gutekunst CA, Rogers D, Warby S, Graham RK, Loubser O, van Raamsdonk J, Singaraja R, Yang YZ, Gafni J, Bredesen D, Hersch SM, Leavitt BR, Roy S, Nicholson DW, Hayden MR.

J Neurosci. 2002 Sep 15;22(18):7862-72.


Partial resistance to malonate-induced striatal cell death in transgenic mouse models of Huntington's disease is dependent on age and CAG repeat length.

Hansson O, Castilho RF, Korhonen L, Lindholm D, Bates GP, Brundin P.

J Neurochem. 2001 Aug;78(4):694-703.


P38 MAPK is involved in enhanced NMDA receptor-dependent excitotoxicity in YAC transgenic mouse model of Huntington disease.

Fan J, Gladding CM, Wang L, Zhang LY, Kaufman AM, Milnerwood AJ, Raymond LA.

Neurobiol Dis. 2012 Mar;45(3):999-1009. doi: 10.1016/j.nbd.2011.12.019. Epub 2011 Dec 14.


Transgenic mice expressing caspase-6-derived N-terminal fragments of mutant huntingtin develop neurologic abnormalities with predominant cytoplasmic inclusion pathology composed largely of a smaller proteolytic derivative.

Tebbenkamp AT, Green C, Xu G, Denovan-Wright EM, Rising AC, Fromholt SE, Brown HH, Swing D, Mandel RJ, Tessarollo L, Borchelt DR.

Hum Mol Genet. 2011 Jul 15;20(14):2770-82. doi: 10.1093/hmg/ddr176. Epub 2011 Apr 22.


p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin.

Ehrnhoefer DE, Skotte NH, Ladha S, Nguyen YT, Qiu X, Deng Y, Huynh KT, Engemann S, Nielsen SM, Becanovic K, Leavitt BR, Hasholt L, Hayden MR.

Hum Mol Genet. 2014 Feb 1;23(3):717-29. doi: 10.1093/hmg/ddt458. Epub 2013 Sep 18.


Interactome network analysis identifies multiple caspase-6 interactors involved in the pathogenesis of HD.

Riechers SP, Butland S, Deng Y, Skotte N, Ehrnhoefer DE, Russ J, Laine J, Laroche M, Pouladi MA, Wanker EE, Hayden MR, Graham RK.

Hum Mol Genet. 2016 Apr 15;25(8):1600-18. doi: 10.1093/hmg/ddw036. Epub 2016 Feb 11.


Glutathione redox cycle dysregulation in Huntington's disease knock-in striatal cells.

Ribeiro M, Rosenstock TR, Cunha-Oliveira T, Ferreira IL, Oliveira CR, Rego AC.

Free Radic Biol Med. 2012 Nov 15;53(10):1857-67. doi: 10.1016/j.freeradbiomed.2012.09.004. Epub 2012 Sep 14.


Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin.

Tanaka Y, Igarashi S, Nakamura M, Gafni J, Torcassi C, Schilling G, Crippen D, Wood JD, Sawa A, Jenkins NA, Copeland NG, Borchelt DR, Ross CA, Ellerby LM.

Neurobiol Dis. 2006 Feb;21(2):381-91. Epub 2005 Sep 16.


Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease.

Zeron MM, Hansson O, Chen N, Wellington CL, Leavitt BR, Brundin P, Hayden MR, Raymond LA.

Neuron. 2002 Mar 14;33(6):849-60.

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