Hsp60, amateur chaperone in amyloid-beta fibrillogenesis.
Biochim Biophys Acta
; 1860(11 Pt A): 2474-2483, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27474204
ABSTRACT
BACKGROUND:
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 Aß peptide and in vivo studies reveal that treatment with specific chaperones or their overexpression can ameliorate some distinct pathological signs characterizing AD.METHODS:
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 Aß fibrillogenesis.RESULTS:
We found that Hsp60 powerfully inhibits Aß amyloid aggregation, by closing molecular pathways leading to peptide fibrillogenesis.CONCLUSIONS:
We observe that Hsp60 inhibits Aß 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. GENERALSIGNIFICANCE:
Understanding the specificity of the molecular interactions of Hsp60 with amyloid Aß peptide allowed us to emphasize the important aspects to be taken into consideration when considering the recent promising therapeutic strategies for neurodegeneration.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Chaperonina 60
/
Amiloide
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article