dc.contributor.author |
Jung, Alisha |
en |
dc.contributor.author |
Fitzsimons, HL |
en |
dc.contributor.author |
Bland, RJ |
en |
dc.contributor.author |
During, Matthew |
en |
dc.contributor.author |
Young, Deborah |
en |
dc.date.accessioned |
2012-03-20T22:38:25Z |
en |
dc.date.issued |
2008 |
en |
dc.identifier.citation |
Molecular Therapy 16(6):1048-1055 01 Jun 2008 |
en |
dc.identifier.issn |
1525-0016 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/14732 |
en |
dc.description.abstract |
Defects in cellular quality control mechanisms are thought to contribute to the neuropathology of Parkinson’s disease (PD). Overexpressing heat shock proteins (HSPs) may constitute a powerful therapeutic strategy for PD, because they boost the ability of the cell to eliminate unwanted proteins. We investigated the neuroprotective potential of HSP70, HSP40, and H-BH, a constitutively active form of heat shock factor 1, in a rat model of PD based on adenoassociated virus (AAV) vector–mediated overexpression of CDCrel-1, a parkin substrate known to be toxic to dopaminergic neurons. AAV vector–mediated overexpression of H-BH and of HSP70 afforded similar levels of protection against CDCrel-1 toxicity, with ~20% improvement in survival of dopaminergic neurons as compared to the controls. The assessment of protection conferred was made using tyrosine hydroxylase (TH) and HuC/D immunohistochemistry and Fluoro-Gold retrograde tracing, and by observing the extent of preservation of spontaneous function and also the extent of drug-induced motor function. In contrast to H-BH and HSP70, HSP40 overexpression exacerbated CDCrel-1-mediated cell death. Realtime reverse transcriptase (RT)-PCR analysis showed that H-BH had the effect of upregulating endogenous HSP70 and HSP40 mRNA levels 10-fold and 4-fold over basal levels, respectively, whereas AAV vector–mediated HSP70 and HSP40 mRNA levels were over 100-fold higher. Our results suggest that a comparatively modest upregulation of multiple HSPs may be an effective approach for achieving significant neuroprotection in PD. |
en |
dc.publisher |
Nature Publishing Group |
en |
dc.relation.ispartofseries |
Molecular Therapy |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from: http://www.sherpa.ac.uk/romeo/issn/1525-0016/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
HSP70 and constitutively active HSF1 mediate protection against CDCrel-1-mediated toxicity |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1038/mt.2008.68 |
en |
pubs.issue |
6 |
en |
pubs.begin-page |
1048 |
en |
pubs.volume |
16 |
en |
dc.rights.holder |
Copyright: Nature Publishing Group |
en |
dc.identifier.pmid |
18398426 |
en |
pubs.end-page |
1055 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
82173 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Pharmacology |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
18398426 |
en |