Nanobodies raised against monomeric É-synuclein inhibit fibril formation and destabilize toxic oligomeric species.
BMC Biol
; 15(1): 57, 2017 07 03.
Article
em En
| MEDLINE
| ID: mdl-28673288
ABSTRACT
BACKGROUND:
The aggregation of the protein É-synuclein (ÉS) underlies a range of increasingly common neurodegenerative disorders including Parkinson's disease. One widely explored therapeutic strategy for these conditions is the use of antibodies to target aggregated ÉS, although a detailed molecular-level mechanism of the action of such species remains elusive. Here, we characterize ÉS aggregation in vitro in the presence of two ÉS-specific single-domain antibodies (nanobodies), NbSyn2 and NbSyn87, which bind to the highly accessible C-terminal region of ÉS.RESULTS:
We show that both nanobodies inhibit the formation of ÉS fibrils. Furthermore, using single-molecule fluorescence techniques, we demonstrate that nanobody binding promotes a rapid conformational conversion from more stable oligomers to less stable oligomers of ÉS, leading to a dramatic reduction in oligomer-induced cellular toxicity.CONCLUSIONS:
The results indicate a novel mechanism by which diseases associated with protein aggregation can be inhibited, and suggest that NbSyn2 and NbSyn87 could have significant therapeutic potential.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Alfa-Sinucleína
/
Anticorpos de Domínio Único
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article