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Antioxid Redox Signal. 2011 Apr 15;14(8):1437-48. doi: 10.1089/ars.2010.3596. Epub 2011 Jan 8.

Redox regulation of the intrinsic pathway in neuronal apoptosis.

Author information

1
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 Green St., Athens, GA 30602, USA. jlfrankl@rx.uga.edu

Abstract

Two principal pathways exist by which cells can undergo apoptotic death, known as the extrinsic and the intrinsic pathways. Binding of a ligand to a death receptor activates the extrinsic pathway. In the intrinsic pathway, an apoptotic stimulus, such as neurotrophin withdrawal or exposure to a toxin, causes a proapoptotic member of the Bcl-2 family of proteins, such as Bax, to permeabilize the outer mitochondrial membrane. This allows redistribution of cytochrome c from the mitochondrial intermembrane space into the cytoplasm, where it causes activation of caspase proteases and, subsequently, cell death. A dramatic increase occurs in mitochondria-derived reactive oxygen species (ROS) during the apoptotic death of sympathetic, cerebellar granule, and cortical neurons. These ROS lie downstream of Bax in each cell type. Here I review possible mechanisms by which Bax causes increased ROS during neuronal apoptosis. I also discuss evidence that these ROS are an important part of the apoptotic cascade in these cells. Finally, I discuss evidence that suggests that neurotrophins prevent release of cytochrome c in neurons through activation of an antioxidant pathway.

PMID:
20812874
PMCID:
PMC3061193
DOI:
10.1089/ars.2010.3596
[Indexed for MEDLINE]
Free PMC Article

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