Therapeutic effects of cystamine in a murine model of Huntington's disease

被引：0

作者：

Dedeoglu, A

Kubilus, JK

Jeitner, TM

Matson, SA

Bogdanov, M

Kowall, NW

Matson, WR

Cooper, AJL

Ratan, RR

Beal, MF

Hersch, SM

Ferrante, RJ

机构：

[1] Bedford Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Unit 182B, Bedford, MA 01730 USA

[2] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[3] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA

[4] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA

[5] ESA Labs Inc, Chelmsford, MA 01824 USA

[6] Cornell Univ, Presbyterian Hosp, Weill Med Coll, Dept Biochem, New York, NY 10021 USA

[7] Cornell Univ, Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA

[8] Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA

[9] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA

[11] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA

[12] Massachusetts Gen Hosp, Neurol Serv, Ctr Aging Genet & Neurodegenerat, Boston, MA 02129 USA

[13] Harvard Univ, Sch Med, Boston, MA 02129 USA

来源：

JOURNAL OF NEUROSCIENCE | 2002年 / 22卷 / 20期

关键词：

Huntington's disease; cystamine; transglutaminase; glutamyl lysine; neuroprotection; transgenic R6/2 mice;

D O I：

暂无

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The precise cause of neuronal death in Huntington's disease (HD) is unknown. Proteolytic products of the huntingtin protein can contribute to toxic cellular aggregates that may be formed in part by tissue transglutaminase (Tgase). Tgase activity is increased in HD brain. Treatment in R6/2 transgenic HD mice, using the transglutaminase inhibitor cystamine, significantly extended survival, improved body weight and motor performance, and delayed the neuropathological sequela. Tgase activity and N-Sigma-(gamma-L-glutamyl)-L-lysine (GGEL) levels were significantly altered in HD mice. Free GGEL, a specific biochemical marker of Tgase activity, was markedly elevated in the neocortex and caudate nucleus in HD patients. Both Tgase and GGEL immunoreactivities colocalized to huntingtin aggregates. Cystamine treatment normalized transglutaminase and GGEL levels in R6/2 mice. These findings are consistent with the hypothesis that transglutaminase activity may play a role in the pathogenesis of HD, and they identify cystamine as a potential therapeutic strategy for treating HD patients.

引用

页码：8942 / 8950

页数：9

共 56 条

[1] Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease [J].