title: The collagen chaperone HSP47 is a new interactor of APP that affects the levels of extracellular beta-amyloid peptides.
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.
authors.affiliation: Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, University of Torino, Torino, Italy.
authors.forename: Federico T
authors.initials: FT
authors.lastname: Bianchi
authors.forename: Paola
authors.initials: P
authors.lastname: Camera
authors.forename: Ugo
authors.initials: U
authors.lastname: Ala
authors.forename: Daniele
authors.initials: D
authors.lastname: Imperiale
authors.forename: Antonio
authors.initials: A
authors.lastname: Migheli
authors.forename: Enrica
authors.initials: E
authors.lastname: Boda
authors.forename: Filippo
authors.initials: F
authors.lastname: Tempia
authors.forename: Gaia
authors.initials: G
authors.lastname: Berto
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Bosio
authors.forename: Salvatore
authors.initials: S
authors.lastname: Oddo
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
authors.forename: Stefano
authors.initials: S
authors.lastname: Taraglio
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Dotti
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D050958:HSP47 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018832:Molecular Chaperones; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D058225:Plaque, Amyloid; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D003432:Cross-Linking Reagents; D050958:HSP47 Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003094:Collagen