期刊
JOURNAL OF NEUROCHEMISTRY
卷 82, 期 6, 页码 1424-1434出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1471-4159.2002.01088.x
关键词
AIDS; apoptosis; CEP-1347; HIV-1 gp120IIIB; MLK3; neuron
资金
- NIDA NIH HHS [DA012121, DA13141] Funding Source: Medline
- NIDDK NIH HHS [DK44840] Funding Source: Medline
- NIMH NIH HHS [MH40165] Funding Source: Medline
- NINDS NIH HHS [NS21442, NS33826] Funding Source: Medline
Overexpression of gp120, the major coat protein of the HIV-1 virus, in central glial cells, or treatment of neurons with gp120 in culture, produces apoptotic neuronal death. Here we demonstrate that CEP-1347 (KT7515), an inhibitor of mixed lineage kinase 3 (MLK3), an upstream activator of JNK, inhibits gp120IIIB-induced apoptosis of hippocampal neurons. Furthermore, expression of wild type MLK3 in hippocampal pyramidal neurons enhanced gp120IIIB-induced neurotoxicity, whereas expression of a dominant negative MLK3 protected neurons from the toxic effects of the glycoprotein. These results indicate a role for MLK3 signaling in gp120IIIB-induced neuronal death, and suggest potential clinical utility of CEP-1347 in inhibiting the progression of AIDS dementia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据