2008 Grants - Li

Modulation of the Gamma-Secretase Complex and Activity by Individual Subunits

Yueming Li, Ph.D.
Sloan-Kettering Institute for Cancer Research
New York, New York

2008 Investigator-Initiated Research Grant

Alzheimer's disease is characterized by the accumulation of the protein fragment beta-amyloid. Scientists believe this fragment disrupts cell-to-cell communication and causes brain cell death in Alzheimer's. Beta-amyloid is clipped from its parent molecule in a two-stage process. The second cut is made by gamma-secretase, a complex of several proteins. One group of gamma-secretase proteins, the presenilin group, is encoded by various PS genes. Mutations in the PS1 and PS2 genes are associated with a greater risk of obtaining familial, or inherited, Alzheimer's. However, other gamma-secretase components likely play important roles in Alzheimer development.

Yueming Li, Ph.D., and colleagues hypothesize that mutated PS1 and PS2 genes work with other gamma-secretase components to promote excessive beta-amyloid production. For this grant, the researchers plan to test their hypothesis using cultured cells.

Results from Dr. Li's study could help clarify the biological mechanisms underlying toxic beta-amyloid production. Such knowledge could lead to novel therapies for treating Alzheimer's disease at its earliest stages.