Affiliations: [a] Department of Pathology, University of Virginia, Charlottesville, VA, USA | [b] Biochemistry and Molecular Genetics and Chemistry, University of Virginia, Charlottesville, VA, USA | [c] IRP, NIMH, NIH, Bethesda, MD, USA | [d] Departments of Biology and Chemistry, Liberty University, Lynchburg, VA, USA
Correspondence:
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Corresponding author: Dr. John Savory, Department of Pathology, University of Virginia Health Sciences Center, Box 168, Charlottesville, Virginia 22908 USA. Tel.: +1 804 924 5682; Fax: +1 804 924 5718; E-mail: js2r@virginia.edu.
Abstract: Neurodegenerative diseases including Alzheimer's disease are characterized by a progressive and selective neuronal loss via an apoptosis mechanism, and there is a growing body of evidence which supports a central role of mitochondria in this apoptotic cell death. Release of cytochrome c from the mitochondria to the cytosol is considered a critical step in apoptosis. Here we report that aluminum maltolate induces cytochrome c translocation into the cytosol as early as 3 hours in aged but not in young rabbit hippocampus. Pretreatment with cyclosporin A, an inhibitor of the mitochondria permeability transition pore (MTP), blocks cytochrome crelease. Therefore, it appears that aluminum maltolate-induced cytochrome c release results from opening of the MTP. This effect implicates aging as a prerequisite factor, since the MTP does not open in young animals. Mitochondrial injury thus may represent a primary initiator of neurodegeneration.
