Amyloid β 42 mutant fibrils
Title: Amyloid β 42 mutant fibrils
SNIC Project: SNIC 2022/5-171
Project Type: SNIC Medium Compute
Principal Investigator: Sara Linse <sara.linse@biochemistry.lu.se>
Affiliation: Lunds universitet
Duration: 2022-05-30 – 2023-06-01
Classification: 10602
Keywords:

Abstract

Alzheimer’s disease affects nearly 50 million people worldwide, and considerable efforts are spent to find both its causes and means for therapeutic intervention. The current hypothesis relates death of neurons to transient oligomeric structures formed during the aggregation of amyloid beta peptide (Aβ). Secondary nucleation is the process that leads to the multiplication and propagation of aggregates, whereby short-lived oligomeric intermediates cause neurotoxicity. During secondary nucleation, fibrils provide catalytic surfaces for the growth of monomers. Understanding the catalytic activity is a fundamental goal in elucidating the molecular mechanisms of Alzheimer’s and associated diseases. Hence elucidating the structure of the 4S mutant fibril, which is incompatible in catalysing the WT monomer, would provide insight into the molecular events that transpire during propagation of aggregates during secondary nucleation.