Autophagy in cancer and neurodegeneration

Autophagy is implicated in adaptive response of cells to provide nutrients and energy upon exposure to stress conditions. Cancer cells are known to undergo various forms of stress, including oncogenic (Ras signaling), metabolic (hypoxia and starvation), and therapeutic (drug treatment) stress, and are dependent on autophagy to clear damaged structures, and to restore metabolic and homeostatic balance. Inhibition of autophagy by siRNA and lysosomal inhibitors (e.g. hydroxychloroquine) has been associated with anti-tumor activities in preclinical models and in the clinic. We are currently engaged in developing tools to selectively regulate autophagy in cancer cells.

Neurodegenerative disorders represent major challenges in clinical medicine owing to their increasing incidence and the lack of effective therapies. Our identification of the autophagy-related protein TECPR2 in association with the neurodegenerative syndrome HSP and possibly others provides a molecular link between autophagy and neurodegeneration. Our research has the potential to contribute significant new knowledge regarding the molecular activity both of TECPR2 and of certain ATG8 family proteins, all critical components of autophagy. With regard to the deregulation of autophagic processes in neurodegenerative diseases, we believe that knowledge gained from this study may promote the development of better diagnostic tools and the design of novel drugs that specifically target these processes.