Appoptosin is a novel pro-apoptotic protein and mediates cell death in neurodegeneration.
Appoptosin is a novel pro-apoptotic protein and mediates cell death in neurodegeneration.
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Appoptosin 是一种新型促凋亡蛋白，可介导神经变性中的细胞死亡
DOI：
10.1523/jneurosci.3668-12.2012
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发表时间：
2012-10-31
期刊：
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
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作者：
Zhang H;Zhang YW;Chen Y;Huang X;Zhou F;Wang W;Xian B;Zhang X;Masliah E;Chen Q;Han JD;Bu G;Reed JC;Liao FF;Chen YG;Xu H
细胞凋亡是多种疾病中必不可少的细胞过程，也是神经退行性变中神经元死亡的主要途径。导致细胞凋亡的详细信号事件/途径，特别是在神经元中，需要进一步阐明。在这里，我们确定了一种β-淀粉样前体蛋白（APP）相互作用蛋白，命名为apoptosin，其水平在阿尔茨海默病和梗死患者的脑样本中上调，在啮齿动物中风模型中，以及在β-淀粉样蛋白（Aβ）和谷氨酸治疗的神经元中。我们进一步证明，凋亡素诱导活性氧释放和内在的半胱天冬酶依赖性细胞凋亡。凋亡素的生理功能是跨线粒体膜转运/交换甘氨酸/5-氨基-乙酰丙酸以合成血红素。凋亡素的下调可防止谷氨酸或Aβ损伤引起的细胞死亡和半胱天冬酶活化。APP通过与凋亡素相互作用调节凋亡素介导的凋亡。我们的研究确定凋亡素作为一个重要的球员在细胞凋亡和一种新的促凋亡蛋白参与神经元细胞死亡，提供了一个可能的新的治疗靶点神经退行性疾病和癌症。
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 proapoptotic protein involved in neuronal cell death, providing a possible new therapeutic target for neurodegenerative disorders and cancers.