Lesson 4: PAK1-blockers=AMPK-activators=HSP-inducers

Among Tyr-kinases essential for the activator of PAK1, FYN plays a unique role. It inactivates the anti-oncogenic kinase LKB1 which in turn inactivates PAK1, and activates the anti-oncogenic kinase AMPK, simultaneously.  Mainly due to this kinase cascade (and a few other signal cascades) , a unique "formula for longevity" has been established at least among herbal compounds, without any exception:  PAK1-blockers=AMPK-activators (1, 2).

The longevity transcription factor "FOXO" is inactivated by PAK1, and activated by AMPK. The FOXO is essential for the expression/induction of a variety of HSP (heat shock protein) genes which protect a variety of intracellular proteins from heat-denaturation or many other stresses. Thus, the higher the HSP level, the longer the healthy lifespan.

In other words, PAK1-blockers=AMPK-activators=HSP-inducers.  Thus, using a unique strain called CL2070 of C. elegans which carries a transgenic gene called HSP16-GFP, in a few days we can screen in vivo for a variety of HSP-inducers, which are PAK1-blockers and AMPK-activators as well (3).

References:

1．Maruta H.（2011）Effective neurofibromatosis therapeutics blocking the oncogenic kinase PAK1. Drug Discov. Ther. 5, 266-78.

2．Maruta H. （2014） Herbal Therapeutics that Block the Oncogenic Kinase PAK1: A Practical Approach towards PAK1-dependent Diseases and Longevity. Phytother Res. 28、656-72．

3．Yanase S, Luo Y, Maruta H.（2013）PAK1-deficiency/down-regulation Reduces Brood Size, Activates HSP16.2 Gene and Extends Lifespan in C. elegans. Drug Dev Ther. 7: 29-35.