Cyclosporin A inhibits Al-induced cytochrome c release from mitochondria in aged rabbits

Othman Ghribi, David A. Dewitt, Michael S. Forbes, Ayala Arad, Mary M. Herman, John Savory

Research output: Contribution to journalArticle

19 Scopus citations

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 c release. 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.

Original languageEnglish (US)
Pages (from-to)387-391
Number of pages5
JournalJournal of Alzheimer's Disease
Volume3
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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