PREFERENTIAL INHIBITION OF PRESENILIN-1

摘要

The invention provides methods for determining whether an agent piefeientially inhibits Presenilin-1-compiised ?-secretase relative to Presenilin-2-comprised ?-secretase. The invention also piovides agents that pieferentially inhibit Presenilin-1-comprised y- secietase lelative to Presenilin-2-comprised ?-sectetase, pharmaceutical compositions compiising such compounds, and methods of heating Alzheimer's disease using such compounds. The invention also discloses that the N-terminal domain of presenilis 1 and -2 determines the difference in the production of Aß by PS1-comprised and PS2-comprised gamma secretases. This finding identified the structuial determinant for the observed difference in the production of Aß by PS1-comprised and PS2-comprised gamma secretases. Such structural deteiminant was not identified before This invention also provides a method foi deteimining whether an agent specifically binds the N terminus of PS1 The invention further provides for methods of treatment of Alzheimer's Disease by administration of an effective dose of an agent which specifically binds PSl , thereby inhibiting PS1 activity