University of California Irvine, (UCI)

nteraction of Amyloid Oligomers with Membranes: Pathogenesis and Therapeutics

Research Area
Aging

Grant Type
Network

Year
2006

Abstract

The purpose of this network grant is to understand how neurons degenerate in amyloid-related degenerative diseases such Alzheimer’s disease, Parkinson’s and age-related macular degeneration and to devise therapeutic strategies to prevent the degeneration. Our hypothesis is that the basic mechanisms of neurodegeneration in these diseases (and probably most other neurodegenerative diseases) is likely to be very similar, so understanding one provides insights into the causes of the other diseases. We discovered that amyloid oligomers permeabilize cellular and artificial membranes and that this property may represent the primary mechanism of amyloid pathogenesis in age related amyloid degenerative diseases.

The current Network program is focused on membrane permeabilization by amyloid oligomers with the goal of developing therapeutic strategies that target disease mechanisms. The aims are to determine the structure of amyloid oligomers, how amyloid oligomers associate with membranes and to search for inhibitors of oligomer formation, membrane permeabilization and inhibitors of amyloid oligomer toxicity. The results of this network research may not only clarify how the disease develops and progresses, but may also identify novel drugs and vaccines to prevent neurodegenerative disease. Our results indicate that the underlying mechanisms of pathogenesis in neurodegenerative diseases are related and also raise the possibility that a treatment against one disease might also be effective against other neurodegenerative diseases.