This article is part of the supplement: Proceedings of the 2011 International Conference on Molecular Neurodegeneration

Open Access Lecture presentation

Identifying an APP-binding protein in neuronal cell death

Yunwu Zhang1* and Huaxi Xu2

  • * Corresponding author: Yunwu Zhang

Author Affiliations

1 Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, College of Medicine, Xiamen University, Xiamen, Fujian 361005, China

2 Neurodegenerative Disease Research Program, Sanford-Burnham Medical Research Institute, La Jolla, California, USA

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Molecular Neurodegeneration 2012, 7(Suppl 1):L22 doi:10.1186/1750-1326-7-S1-L22


The electronic version of this article is the complete one and can be found online at: http://www.molecularneurodegeneration.com/content/7/S1/L22


Published:7 February 2012

© 2012 Zhang and Xu; licensee 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.

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.