Strategic role for mitochondria in Alzheimer's disease and cancer

Detailed knowledge about cell death and cell survival mechanisms and how these pathways are impaired in neurodegenerative disorders and cancer forms the basis for future drug development for these diseases that affect millions of people around the world.

In neurodegenerative disorders such as Alzheimer's disease (AD), cell death pathways are inappropriately activated, resulting in neuronal cell death. In contrast, cancer cells develop resistance to apoptosis by regulating anti-apoptotic proteins signaling via mitochondria. Mounting evidence shows that mitochondrial function is central in both cancer and AD. Cancer cells typically shut down oxidative phosphorylation (OXPHOS) in mitochondria and switch to glycolysis for ATP production, making them resistant to hypoxia. In AD, for example, amyloid-β peptide (Aβ) and reactive oxygen species impair mitochondrial function. Neurons therefore also switch to glycolysis to maintain ATP production and to produce molecules involved in antioxidant metabolism in an attempt to survive.

One critical difference between cancer cells and neurons is that cancer cells can survive without OXPHOS, while neurons are dependent on OXPHOS for long-term survival.

This review will focus on these abnormalities of mitochondrial function shared in AD and cancer and discuss the potential mechanisms underlying links that may be key steps in the development of therapeutic strategies.