Neurotoxic effects of the HCV core protein are mediated by sustained activation of ERK via TLR2 signaling.
J Neurovirol
; 17(4): 327-40, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21660601
ABSTRACT
Hepatitis C virus (HCV) infection is a serious problem among those co-infected with human immunodeficiency virus; however, its impact in the central nervous system (CNS) remains unclear. This study aimed to investigate the mechanisms underlying HCV core protein-mediated neurodegeneration. Analysis of human HCV seropositive cases demonstrated widespread damage to neuronal dendritic processes and sustained activation of extracellular signal-related kinase (ERK); analogous pathologies were observed in wild type injected with HCV core protein into the hippocampus. In vitro analysis in neuronal cells exposed to HCV core demonstrated retraction of the neuronal processes in an ERK/Signal Transducer and Activator of Transcription 3 (STAT3)-dependent manner dependent on toll-like receptor 2 (TLR2) signaling activation. These results indicate that HCV core protein neurotoxicity may be mediated by the sustained activation of ERK/STAT3 via TLR2-IRAK1 signaling pathway. These pathways provide novel targets for development of neuroprotective treatments for HCV involvement of the CNS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatite C
/
Hepacivirus
/
MAP Quinase Quinase Quinases
/
Sistema de Sinalização das MAP Quinases
/
Fator de Transcrição STAT3
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Receptor 2 Toll-Like
/
Quinases Associadas a Receptores de Interleucina-1
Idioma:
En
Revista:
J Neurovirol
Ano de publicação:
2011
Tipo de documento:
Article