Transgenic mice expressing a dominant negative mutant interleukin-1β converting enzyme show resistance to MPTP neurotoxicity

被引:68
作者
Klevenyi, P
Andreassen, O
Ferrante, RJ
Schleicher, JR
Friedlander, RM
Beal, MF
机构
[1] Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA 02114 USA
[3] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
[4] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA
[5] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA
[6] Dept Vet Affairs, Bedford, MA USA
[7] Brigham & Womens Hosp, Dept Surg, Neurosurg Serv, Boston, MA 02115 USA
关键词
apoptosis; caspases; dopamine; MPTP; Parkinson's disease;
D O I
10.1097/00001756-199902250-00035
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
INCREASING evidence implicates apoptosis as a major mechanism of cell death in neurodegenerative diseases. Recent evidence has demonstrated that chronic administration of MPTP can lead to apoptotic cell death. In the present study we examined whether transgenic mice expressing a dominant negative inhibitor of interleukin-1 beta convertase enzyme (ICE) are resistant to MPTP induced neurotoxicity. MPTP resulted in a significant depletion of dopamine, DOPAC and HVA in littermate control mice which were completely inhibited in the mutant interleukin-1 beta converting enzyme mice. There was also significant protection against MPTP-induced depletion of tyrosine hydroxylase-immunoreactive neurons. There was no alteration in MPTP uptake or metabolism. These results provide further evidence that apoptotic cell death as well as ICE may play an important role in the neurotoxicity of MPTP. (C) 1999 Lippincott Williams & Wilkins.
引用
收藏
页码:635 / 638
页数:4
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