. Quantitative interaction proteomics of neurodegenerative disease proteins. Cell Rep. 2015 May 19;11(7):1134-46. Epub 2015 May 7 PubMed.


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  1. The report of Hosp and colleagues describes an elegant and novel method for quantitative interaction proteomics with the identification of multiple interactors for neurodegenerative disease associated proteins. A limitation of the approach, as the authors point out, is that it initially requires overexpression of the bait protein by transfection. However, a number of the interactors were subsequently validated by analysis of endogenously expressed proteins. One the most interesting interactions is between APP and LRPPRC, a central regulator of mitochondrial gene expression. This raises the intriguing possibility that mutations and copy number variants of APP that give rise to AD may act in part through mitochondrial dysregulation.

    This report provides many potential avenues for future investigation. More broadly, interaction proteomics provides a general and much-needed approach for rapid functional characterization of disease-related genes emerging from GWAS and exome sequencing studies. To validate this approach, follow-up studies using mouse models and other model systems will be needed to confirm the disease relevance of the newly identified interactors.

    View all comments by Bruce Yankner

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