title: Hsp60, amateur chaperone in amyloid-beta fibrillogenesis.
abstract: Molecular chaperones are a very special class of proteins that play essential roles in many cellular processes like folding, targeting and transport of proteins. Moreover, recent evidence indicates that chaperones can act as potentially strong suppressor agents in Alzheimer's disease (AD). Indeed, in vitro experiments demonstrate that several chaperones are able to significantly slow down or suppress aggregation of Aβ peptide and in vivo studies reveal that treatment with specific chaperones or their overexpression can ameliorate some distinct pathological signs characterizing AD.
  
  
  
  Here we investigate using a biophysical approach (fluorescence, circular dichroism (CD), transmission electron (TEM) and atomic force (AFM) microscopy, size exclusion chromatography (SEC)) the effect of the human chaperonin Hsp60 on Aβ fibrillogenesis.
  
  
  
  We found that Hsp60 powerfully inhibits Aβ amyloid aggregation, by closing molecular pathways leading to peptide fibrillogenesis.
  
  
  
  We observe that Hsp60 inhibits Aβ aggregation through a more complex mechanism than a simple folding chaperone action. The action is specifically directed toward the early oligomeric species behaving as aggregation seeds for on-pathway amyloid fibrillogenesis.
  
  
  
  Understanding the specificity of the molecular interactions of Hsp60 with amyloid Aβ peptide allowed us to emphasize the important aspects to be taken into consideration when considering the recent promising therapeutic strategies for neurodegeneration.
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy.
authors.forename: Maria Rosalia
authors.initials: MR
authors.lastname: Mangione
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy. Electronic address: silvia.vilasi@pa.ibf.cnr.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vilasi
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy; Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA; Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Marino
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Librizzi
authors.affiliation: Nanophysics Department, Istituto Italiano di Tecnologia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Canale
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy; Department of Physics and Chemistry, University of Palermo, Palermo, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Spigolon
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy; Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fucarino
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Passantino
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy; Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Italy; Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Bulone
authors.affiliation: Institute of Biophysics, National Research Council, Palermo, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: San Biagio
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D018834:Chaperonin 60
keywords: Alzheimer's disease treatment; Amyloid aggregation; Chaperonin; Inhibition mechanisms; Molecular chaperones