Molecular mechanism in regulation of the intramembrane proteases

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Since intramenbrane proteases possess these active sites buried in the lipid bilayer, it is difficult to purify and measure their activities. We introduced human gamma-secretase complex in yeast and succeeded in measuring its activity in vitro with the yeast microsomes. In this research, we utilized the reconstition system and analyzed the enzymatic character of the gamma-secretase. We found the relationship between proteolytic activities and subunit composition, and we screened the modulator of the protease activities from lipids and natural compounds. Malfunction of gamma-secretase leads to Alzheimer's disease. We would like to expand our research to the treatment of the disease.