************ The 7th Lab Seminar *************

Linking folding with aggregation in Alzheimer's beta-amyloid
peptides
Jana Khandogin and Charles L. Brooks III
The Proceedings of National Academy of Science of the 
United States of America 104(43) (2007) 16880-16885

Speaker : Yukichi Kitamura

Date : Thu. Jul. 7th, 1:30 pm

Abstract
Growing evidence suggests that the beta-amyloid (Abeta) peptides 
of Alzheimer's disease are generated in early endosomes 
and that small oligomers are the principal toxic species. We
sought to understand whether and how the solution pH, which 
is more acidic in endosomes than the extracellular 
environment, affects the conformational processed of Abeta. 
Using constant pH molecular dynamics simulations of two 
model peptides, Abeta(1-28) and Abeta(10-42), we found that the 
folding landscape of Abeta is strongly modulated by pH and is 
most favorable for hydrophobically driven aggregation at pH 6. 
Thus, our theoretical findings substantiate the possibility that 
Abeta oligomers develop intracellularly before secretion into the 
extracellular milieu, where they may disrupt synaptic activity 
or act as seeds for plaque formation.

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