APS -2017 Annual Meeting of the APS Mid-Atlantic Section- Event - Insights into Cross-Linked Amyloid $eta$-Protein Oligomers and Their Role in Alzheimer's Disease

摘要

Protein misfolding and aberrant protein aggregation are atthe core of many age--triggered diseases, such asAlzheimer's, Parkinson's, and Huntington's disease,amyotrophic lateral sclerosis, type II diabetes, systemicamyloidoses, and others. Proteins associated with thesediseases do not share any obvious aspects of the primarystructure yet they self--assemble into cytotoxiclow--molecular weight oligomers and form fibrils with acommon cross-$eta$ structure. Amyloid $eta$-protein(A$eta$) assembly plays a central role in Alzheimer'sdisease (AD), which is the leading cause of dementia inelderly worldwide. I will describe several computational andexperimental approaches that offer insights into formation ofA$eta$ oligomers under oxidative stress conditionsoccurring in aging brain, which may stabilize A$eta$oligomers, inhibit their structural conversion into amyloidfibrils, and prolong their toxic action. Formation andstructure of cross-linked A$eta$ oligomers may hold akey to understanding the basis of A$eta$ oligomer toxicityand provide clues on how to inhibit their toxic action.