Drug Discovery Utilizing the Autophagy Pathway

  AUTAC (Autophagy-targeting Chimera) is a new class of compounds that leverages a specific protein modification, called S-guanylation, to artificially control the cell's natural "self-cleaning" system, autophagy. This allows AUTAC to precisely target and degrade disease-causing proteins and organelles.This unique mechanism provides an entirely new approach for targeting proteins that have been difficult to address with traditional small-molecule drugs. AUTAC holds significant potential as a new treatment for intractable diseases caused by the accumulation of abnormal proteins, such as cancer and neurodegenerative disorders.A key feature of AUTAC is that it utilizes a different degradation pathway from the existing ubiquitin-proteasome system. This distinction means that it may be able to degrade not only proteins but also viruses, bacteria, and even intracellular organelles.Our lab is also engaged in fundamental research to elucidate the basic mechanisms of S-guanylation-initiated autophagy, which strengthens the theoretical foundation of AUTAC technology. Through this combination of fundamental and applied research, AUTAC is attracting considerable attention as a revolutionary platform for the development of next-generation drugs.

Elucidating Aging and Longevity Mechanisms Using the Nematode C. elegans

  The nematode Caenorhabditis elegans is an ideal model organism for aging research used worldwide. This is due to its short life span of just 2-3 weeks, its transparent body structure which makes it easy to observe, and the simplicity of genetic manipulation. Using C. elegans, our lab has shown that autophagy plays a central role in extending life span. A particularly important discovery we made is that the compound 8-nitro-cGMP extends life span by activating autophagy. Other studies have also shown that various interventions—such as calorie restriction, manipulation of specific genes (like daf-2), and administering compounds like N-acetylglucosamine and spermidine—all extend life span by converging on and activating the autophagy pathway. The fact that these diverse approaches all lead to the same pathway highlights the foundational importance of autophagy in the aging process. Our discovery of 8-nitro-cGMP, in particular, opens up new possibilities for controlling longevity through chemical intervention and is expected to lead to the development of comprehensive anti-aging strategies that combine multiple approaches.