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- Title
Appoptosin is a Novel Pro-Apoptotic Protein and Mediates Cell Death in Neurodegeneration.
- Authors
Han Zhang; Yun-wu Zhang; Yaomin Chen; Xiumei Huang; Fangfang Zhou; Weiwei Wang; Bo Xian; Xian Zhang; Masliah, Eliezer; Quan Chen; Han, Jing-Dong J.; Guojun Bu; Reed, John C.; Liao, Francesca-Fang; Ye-Guang Chen; Huaxi Xu
- 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 β-amyloid precur-sor 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 β-amyloid (Aβ) and glutamate. We further demon-strate 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. Downregu-lation of appoptosin prevents cell death and caspase activation caused by glutamate or Aβ 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.
- Subjects
NEUROLOGICAL research; APOPTOSIS; NEUROLOGICAL emergencies; NEURODEGENERATION; NEURAL pathways; AMYLOID; REACTIVE oxygen species; GLUTAMIC acid
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 44, p15565
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3668-12.2012