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Appoptosin is a Novel Pro-Apoptotic Protein and Mediates Cell Death in Neurodegeneration

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Date
2012-10-31
Author
Zhang, Han
Zhang, Yun-wu
Chen, Yaomin
Huang, Xiumei
Zhou, Fangfang
Wang, Weiwei
Xian, Bo
Zhang, Xian
Masliah, Eliezer
Chen, Quan
Han, Jing-Dong J.
Bu, Guojun
Reed, John C.
Liao, Francesca
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  • 生物医学-已发表论文 [114]
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Abstract
Apoptosis is an essential cellular process in multiple diseases and a major pathway for neuronal death in neurodegeneration. The detailed signaling events/pathways leading to apoptosis, especially in neurons, require further elucidation. Here we identify a beta-amyloid precursor protein (APP)-interacting protein, designated as appoptosin, whose levels are upregulated in brain samples from Alzheimer's disease and infarct patients, and in rodent stroke models, as well as in neurons treated with beta-amyloid (A beta) and glutamate. We further demonstrate that appoptosin induces reactive oxygen species release and intrinsic caspase-dependent apoptosis. The physiological function of appoptosin is to transport/exchange glycine/5-amino-levulinic acid across the mitochondrial membrane for heme synthesis. Downregulation of appoptosin prevents cell death and caspase activation caused by glutamate or A beta insults. APP modulates appoptosin-mediated apoptosis through interaction with appoptosin. Our study identifies appoptosin as a crucial player in apoptosis and a novel pro-apoptotic protein involved in neuronal cell death, providing a possible new therapeutic target for neurodegenerative disorders.
Description
National Institutes of Health [R01AG038710, R01AG021173, R01NS046673, R01AG030197, R03AG034366, R01NS054880, R01AG031893, AG5131, AG18440, R21AG038968]; Alzheimer's Association; American Health Assistance Foundation; National Natural Science Foundation of China [30840036, 30973150, 30921004, 30930050]; National Basic Research Program of China [2010CB833706]; 973 Prophase Project [2010CB535004]; Natural Science Foundation of Fujian Province of China [2009J06022, 2010J01233, 2010J01235]; Program for New Century Excellent Talents in Universities; Fundamental Research Funds for the Central Universities; Fok Ying Tung Education Foundation
Citation
Journal of Neuroscience, 2012,32(44):15565-15576
URI
https://dspace.xmu.edu.cn/handle/2288/66033

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