The collagen chaperone HSP47 is a new interactor of APP that affects the levels of extracellular Beta-Amyloid peptides

Federico T. Bianchi, Paola Camera, Ugo Ala, Daniele Imperiale, Antonio Migheli, Enrica Boda, Filippo Tempia, Gaia Berto, Ylenia Bosio, Salvatore Oddo, Frank M. LaFerla, Stefano Taraglio, Carlos G. Dotti, Ferdinando Di Cunto

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques.

Original languageEnglish (US)
Article numbere22370
JournalPloS one
Volume6
Issue number7
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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