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Searching For Amyloid Interactions

Date:
January 25, 2008
Source:
American Society for Biochemistry and Molecular Biology
Summary:
Researchers have undertaken a large-scale investigation into the molecular environment of the amyloid precursor protein (APP), a protein centrally associated with Alzheimer's disease.
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Researchers have undertaken a large-scale investigation into the molecular environment of the amyloid precursor protein (APP), a protein centrally associated with Alzheimer's disease.

A defining hallmark of Alzheimer's is the extracellular accumulation of amyloid plaques in the diseased brain. These plaques arise from the cleavage of APP, which generates short, sticky fragments called amyloid B-peptides. Despite intense research efforts, however, the function of APP remains enigmatic and only a few proteins are known to interact with it.

Gerold Schmitt-Ulms and colleagues employed a technique called 'time-controlled transcardiac perfusion cross-linking" to uncover more APP-interacting proteins. They pumped a chemical through a mouse's body that would permanently cross-link any proteins that were in close proximity. They could then fish out APP from the brain and study what it was linked to.

From their perfusion, Schmitt-Ulms and colleagues confirmed eight previously reported APP interactions and also identified over 30 new, potentially interacting proteins. They also mapped the interactions of two proteins related to APP that are not known to cause disease, to sense which interactions the three related proteins had in common and which were APP-specific; interestingly the majority of the potential binding partners were specific to APP.

This work constitutes the most comprehensive analysis of the APP interactome to date and may finally shed light on the functional roles of APP in the brain. The researchers believe further investigations of these new interactions may reveal an "Achilles' heel" in the biology of APP that can be exploited for diagnosis or therapy.


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Materials provided by American Society for Biochemistry and Molecular Biology. Note: Content may be edited for style and length.


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American Society for Biochemistry and Molecular Biology. "Searching For Amyloid Interactions." ScienceDaily. ScienceDaily, 25 January 2008. <www.sciencedaily.com/releases/2008/01/080122154805.htm>.
American Society for Biochemistry and Molecular Biology. (2008, January 25). Searching For Amyloid Interactions. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2008/01/080122154805.htm
American Society for Biochemistry and Molecular Biology. "Searching For Amyloid Interactions." ScienceDaily. www.sciencedaily.com/releases/2008/01/080122154805.htm (accessed March 28, 2024).

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