期刊
CELL DEATH AND DIFFERENTIATION
卷 21, 期 5, 页码 696-706出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2013.194
关键词
Alzheimer disease; Caspase-6; cognitive impairment; aging; neurodegeneration
资金
- Canadian Foundation of Innovation
- Canadian Institutes of Health Research (CIHR) [MOP-243413-BCA-CGAG-45097]
- CIHR [MOP-84275]
- National Institute of Aging [P30AG10161, R01AG15819]
Active Caspase-6 is abundant in the neuropil threads, neuritic plaques and neurofibrillary tangles of Alzheimer disease brains. However, its contribution to the pathophysiology of Alzheimer disease is unclear. Here, we show that higher levels of Caspase-6 activity in the CA1 region of aged human hippocampi correlate with lower cognitive performance. To determine whether Caspase-6 activity, in the absence of plaques and tangles, is sufficient to cause memory deficits, we generated a transgenic knock-in mouse that expresses a self-activated form of human Caspase-6 in the CA1. This Caspase-6 mouse develops age-dependent spatial and episodic memory impairment. Caspase-6 induces neuronal degeneration and inflammation. We conclude that Caspase-6 activation in mouse CA1 neurons is sufficient to induce neuronal degeneration and age-dependent memory impairment. These results indicate that Caspase-6 activity in CA1 could be responsible for the lower cognitive performance of aged humans. Consequently, preventing or inhibiting Caspase-6 activity in the aged may provide an efficient novel therapeutic approach against Alzheimer disease.
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