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Identifying an APP-binding protein in neuronal cell death

Background

Apoptosis is an essential cellular process involved in multiple diseases and a major pathway for neuronal death in neurodegeneration. The detailed signaling events/pathways that lead to apoptosis, especially in neurons, require further elucidation.

Results

Here we find that a mitochondrial solute carrier family protein, 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. Alzheimer’s β-amyloid precursor protein interacts with appoptosin and modulates appoptosin-induced apoptosis. Levels of appoptosin are upregulated in brain samples from Alzheimer’s disease and infarct patients and in rodent stroke models, as well as in cells treated with β-amyloid (Aβ) and glutamate. Downregulation of appoptosin prevents the cell death and caspase activation caused by glutamate or Aβ insults.

Conclusion

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.

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Correspondence to Yunwu Zhang.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Zhang, Y., Xu, H. Identifying an APP-binding protein in neuronal cell death. Mol Neurodegeneration 7, L22 (2012). https://doi.org/10.1186/1750-1326-7-S1-L22

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Keywords

  • Neuronal Cell Death
  • Solute Carrier Family
  • Reactive Oxygen Species Release
  • Essential Cellular Process
  • Rodent Stroke