Summary

Plaques and tangles are accumulations of misfolded proteins that form in Alzheimer's disease. These protein aggregates are thought to be toxic to cells in the brain. We have identified a modifier gene that suppresses aggregation of many misfolded proteins. This project outlines experiments to study how this modifier works, and to test its ability to suppress the accumulation of plaques and tangles in animal models of Alzheimer's disease.

Project Details

Plaques and tangles are accumulations of misfolded proteins which form in Alzheimer's disease. These protein aggregates are thought to be toxic to cells in the brain. Although the proteins are expressed in most cells in the brain, only some cells form aggregates of proteins and die. Investigating why some cells are affected and others are not may lead to therapies that suppress the formation of harmful aggregates in nerve cells that are affected by Alzheimer's disease. We have identified a novel model of neurodegeneration that is caused by aggregation of many different proteins and a previously uncharacterized modifier gene that suppresses aggregation of these proteins. This model provides the opportunity to determine why some neurons form aggregates and others are unaffected. We hypothesize that increased expression of this modifier gene will help nerve cells to dispose of misfolded proteins that form aggregates in Alzheimer's disease. We are testing the effect of both the deletion and increased expression of the modifier gene on the ability of cells to suppress the accumulation of plaques and tangles in animal models of Alzheimer's disease. The modifier is a novel gene with unknown function and its ability to suppress aggregates of many different proteins may lead to novel therapeutic agents for Alzheimer's disease and other neurodegenerative diseases caused by protein misfolding as well as other diseases, such as cancer, that are impacted by the regulation of protein degradation pathways.