Drug Discovery in the Autophagy Pathways

Autophagy is an evolutionarily conserved lysosomal degradation process, which has drawn increasing attention in recent years for its connections with various human diseases. Although regulation of autophagy is a complex process, a bulk of evidence has demonstrated that the hub genes such as autophagy-related genes (ATGs), PI3 kinase, and mTOR may play key roles in regulating autophagy activity in physiologic or patho-physiologic conditions. Thus, it is conceivable that targeting autophagic pathways may provide a new opportunity for discovery and development of novel drugs for treatment of human diseases such as cancer, neuro-degeneration and cardiovascular diseases. Some autophagy-modulating agents such as rapamycin and chloroquine have already been in clinical use for treatment of cancer. Moreover, the autophagic pathway network-based target identification and structure-based drug screening would provide more precise and promising approaches to drug discovery. Thus, a better understanding of the regulatory mechanism of autophagy will facilitate the exploitation of autophagy as a target for therapeutic intervention of various human diseases.