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

doi:10.1371/journal.pone.0022370

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

PLoS One. 2011;6(7):e22370. doi: 10.1371/journal.pone.0022370. Epub 2011 Jul 28.

Authors

Federico T Bianchi¹, 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

Affiliation

¹ Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, University of Torino, Torino, Italy.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / metabolism*
Alzheimer Disease / pathology*
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism*
Amyloid beta-Protein Precursor / genetics
Amyloid beta-Protein Precursor / metabolism*
Animals
Biomarkers / metabolism
Blotting, Western
Brain / metabolism
Cell Proliferation
Cells, Cultured
Collagen / metabolism
Cross-Linking Reagents / pharmacology
Disease Models, Animal*
Embryo, Mammalian / cytology
Embryo, Mammalian / drug effects
Embryo, Mammalian / metabolism
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Gene Expression Profiling
HSP47 Heat-Shock Proteins / antagonists & inhibitors
HSP47 Heat-Shock Proteins / genetics
HSP47 Heat-Shock Proteins / metabolism*
HeLa Cells
Hippocampus / cytology
Hippocampus / drug effects
Hippocampus / metabolism
Humans
Immunoenzyme Techniques
Immunoprecipitation
Male
Mice
Molecular Chaperones
Neurons / cytology
Neurons / drug effects
Neurons / metabolism
Oligonucleotide Array Sequence Analysis
Plaque, Amyloid*
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction

Substances

Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Biomarkers
Cross-Linking Reagents
HSP47 Heat-Shock Proteins
Molecular Chaperones
RNA, Messenger
RNA, Small Interfering
Collagen