Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease

被引：890

作者：

Chen, M

Ona, VO

Li, MW

Ferrante, RJ

Fink, KB

Zhu, S

Bian, J

Guo, L

Farrell, LA

Hersch, SM

Hobbs, W

Vonsattel, JP

Cha, JHJ

Friedlander, RM ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Neurosurg Serv,Neuroapoptosis Lab, Boston, MA 02115 USA

[2] Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA

[3] Boston Univ, Sch Med, Bedford, MA 01730 USA

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

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

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

[7] Univ Bonn, Sch Med, Dept Pharmacol, D-5300 Bonn, Germany

[8] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA

[9] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA

[10] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA

[11] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathol, Boston, MA 02114 USA

来源：

NATURE MEDICINE | 2000年 / 6卷 / 07期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/77528

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Huntington disease is an autosomal dominant neurodegenerative disease with no effective treatment. Minocycline is a tetracycline derivative with proven safety. After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction. As caspase-1 and nitric oxide seem to play a role in Huntington disease, we evaluated the therapeutic efficacy of minocycline in the R6/2 mouse model of Huntington disease. We report that minocycline delays disease progression, inhibits caspase-1 and caspase-3 mRNA upregulation, and decreases inducible nitric oxide synthetase activity. In addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3 inhibition. This is the first demonstration of caspase-1 and caspase-3 transcriptional regulation in a Huntington disease model.

引用

页码：797 / +

页数：6

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