Peri-nuclear clustering of mitochondria is triggered during aluminum maltolate induced apoptosis.

Synapse loss and neuronal death are key features of Alzheimer's disease pathology. Disrupted axonal transport of mitochondria is a potential mechanism that could contribute to both. As the major producer of ATP in the cell, transport of mitochondria to the synapse is required for synapse maintenance.

Aluminum maltolate-induced toxicity in NT2 cells occurs through apoptosis and includes cytochrome c release.

Aluminum (Al) compounds are neurotoxic and have been shown to induce experimental neurodegeneration although the mechanism of this effect is unclear. In order to study this neurotoxic effect of Al, we have developed an in vitro model system using Al maltolate and human NT2 cells. Al maltolate at 500 microM caused significant cell death with a 24-h incubation and this toxicity was even more evident after 48 h.

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

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.