Neuronal DNA damage correlates with overexpression of interleukin-1beta converting enzyme in APPV717F mice.
Neuronal DNA damage correlates with overexpression of interleukin-1beta converting enzyme in APPV717F mice.
复制标题
APPV717F 小鼠中神经元 DNA 损伤与白细胞介素 1β 转换酶的过度表达相关。
DOI：
10.1016/s0197-4580(01)00298-6
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发表时间：
2001
影响因子：
4.2
通讯作者：
Griffin,WS
中科院分区：
文献类型：
--
作者：
Sheng,JG;Mrak,RE;Jones,RA;Brewer,MM;Zhou,XQ;McGinness,J;Woodward,S;Bales,K;Paul,SM;Cordell,B;Griffin,WS
Transgenic APPV717F mice, homozygous for a human minigene encoding the V717F familial Alzheimer’s disease mutation, develop Aβ plaques similar to those seen in Alzheimer patients and show evidence of neuronal cell drop out in CA2–3 regions of the hippocampus at 8 months of age and older. Interleukin-1 (IL-1)β (IL-1β) converting enzyme (ICE) is a cysteine protease (caspase-1) that processes inactive (33 kDa) pro-IL-1β to the active (17 kDa) inflammatory cytokine. We used immunohistochemistry, RT-PCR, and DNA cleavage (TUNEL) analysis to show progressive, age-associated increases in ICE mRNA levels, in the numbers of ICE-immunoreactive glia, and in the numbers of neurons showing evidence of DNA damage in APPV717F mice that commenced months prior to the appearance of Aβ plaques. Moreover, there were significant correlations between these parameters over an age range of 1–17 months. These findings are consistent with the idea that increases in ICE activity and expression contribute to neuronal injury in Alzheimer’s disease.
