Title
Hsp60, amateur chaperone in amyloid-beta fibrillogenesis
Author
Maria Rosalia Mangione, Silvia Vilasi, Claudia Marino, Fabio Librizzi, Claudio Canale, Dario Spigolon, Fabio Bucchieri, Alberto Fucarino, Rosa Passantino, Francesco Cappello, Donatella Bulone, Pier Luigi San Biagio
Year
2016
Journal
Biochimica et Biophysica Acta (BBA) - General Subjects
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.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Ligand binding, Aggregation, Kinetics, Biochemistry