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01-08-2011

Neurotoxic effects of the HCV core protein are mediated by sustained activation of ERK via TLR2 signaling

Authors: Amy D. Paulino, Kiren Ubhi, Edward Rockenstein, Anthony Adame, Leslie Crews, Scott Letendre, Ronald Ellis, Ian P. Everall, Igor Grant, Eliezer Masliah

Published in: Journal of NeuroVirology | Issue 4/2011

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.

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Title: Neurotoxic effects of the HCV core protein are mediated by sustained activation of ERK via TLR2 signaling
Authors: Amy D. Paulino
Kiren Ubhi
Edward Rockenstein
Anthony Adame
Leslie Crews
Scott Letendre
Ronald Ellis
Ian P. Everall
Igor Grant
Eliezer Masliah
Publication date: 01-08-2011
Publisher: Springer US
Published in: Journal of NeuroVirology / Issue 4/2011
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-011-0039-0

At a glance: The STEP trials

Springer Medicine

Neurotoxic effects of the HCV core protein are mediated by sustained activation of ERK via TLR2 signaling

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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