- Lecture presentation
- Open Access
Identifying an APP-binding protein in neuronal cell death
© Zhang and Xu; licensee BioMed Central Ltd. 2012
- Published: 7 February 2012
- Neuronal Cell Death
- Solute Carrier Family
- Reactive Oxygen Species Release
- Essential Cellular Process
- Rodent Stroke
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.
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.
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.
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.