TY - JOUR
T1 - Appoptosin is a novel pro-apoptotic protein and mediates cell death in neurodegeneration
AU - Zhang, Han
AU - Zhang, Yun wu
AU - Chen, Yaomin
AU - Huang, Xiumei
AU - Zhou, Fangfang
AU - Wang, Weiwei
AU - Xian, Bo
AU - Zhang, Xian
AU - Masliah, Eliezer
AU - Chen, Quan
AU - Han, Jing Dong J.
AU - Bu, Guojun
AU - Reed, John C.
AU - Liao, Francesca Fang
AU - Chen, Ye Guang
AU - Xu, Huaxi
PY - 2012/10/31
Y1 - 2012/10/31
N2 - 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 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 β-amyloid (Aβ) 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 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.
AB - 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 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 β-amyloid (Aβ) 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 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.
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U2 - 10.1523/JNEUROSCI.3668-12.2012
DO - 10.1523/JNEUROSCI.3668-12.2012
M3 - Article
C2 - 23115192
AN - SCOPUS:84868091629
SN - 0270-6474
VL - 32
SP - 15565
EP - 15576
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 44
ER -