Author Topic: Trehalose May Inhibit Aggregation of Alzheimer’s  (Read 2471 times)

Offline JC Spencer

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Trehalose May Inhibit Aggregation of Alzheimer’s
« Reply #1 on: October 07, 2010, 05:18:05 PM »
Comments by J. C. Spencer

Peptide technology and the folding of proteins is a critical phase in the construction and repairing building blocks of the human anatomy as each cell is formed and repairs are made to the body.  Misfolding of proteins is the cause for neurodegenerative diseases.   In October 2010 a paper published of the work conducted at the University of Wisconsin shows that trehalose reduces the conformational change that the peptide undergoes when it inserts into the monolayer. This observation helps explain the experimentally observed elimination of the lag time by trehalose and the temperature dependence of the lag time in the water subphase.

Here is the Abstract.

Biochim Biophys Acta. 2010 Oct 1. [Epub ahead of print]
Effect of trehalose on the interaction of Alzheimer's Aβ-peptide and anionic lipid monolayers.
Izmitli A, Schebor C, McGovern MP, Reddy AS, Abbott NL, de Pablo JJ.
Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI.
Abstract
The interaction of amyloid β-peptide (Aβ) with cell membranes is believed to play a central role in the pathogenesis of Alzheimer's Disease. In particular, recent experimental evidence indicates that bilayer and monolayer membranes accelerate the aggregation and amyloid fibril formation rate of Aβ. Understanding that interaction could help develop therapeutic strategies for treatment of the disease. Trehalose, a disaccharide of glucose, has been shown to be effective in preventing the aggregation of numerous proteins. It has also been shown to delay the onset of certain amyloid-related diseases in a mouse model. Using Langmuir monolayers and molecular simulations of the corresponding system, we study several thermodynamic and kinetic aspects of the insertion of Aβ peptide into DPPG monolayers in water and trehalose subphases. In the water subphase, the insertion of the Aβ peptide into the monolayer exhibits a lag time which decreases with increasing temperature of the subphase. In the presence of trehalose, the lag time is completely eliminated and peptide insertion is completed within a shorter time period compared to that observed in pure water. Molecular simulations show that more peptide is inserted into the monolayer in the water subphase, and that such insertion is deeper. The peptide at the monolayer interface orients itself parallel to the monolayer, while it inserts with an angle of 50° in trehalose subphase. Simulations also show that trehalose reduces the conformational change that the peptide undergoes when it inserts into the monolayer. This observation helps explain the experimentally observed elimination of the lag time by trehalose and the temperature dependence of the lag time in the water subphase.

http://www.ncbi.nlm.nih.gov/pubmed/20920466?dopt=Abstract

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