Direct Visualization of CHIP-Mediated Degradation of Alpha-Synuclein In Vivo: Implications for PD Therapeutics

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Direct Visualization of CHIP-Mediated Degradation of Alpha-Synuclein In Vivo: Implications for PD Therapeutics

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Title: Direct Visualization of CHIP-Mediated Degradation of Alpha-Synuclein In Vivo: Implications for PD Therapeutics
Author: Dimant, Hemi; Zhu, Liya; Kibuuka, Laura N.; Fan, Zhanyun; Hyman, Bradley T.; McLean, Pamela J.

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Citation: Dimant, Hemi, Liya Zhu, Laura N. Kibuuka, Zhanyun Fan, Bradley T. Hyman, and Pamela J. McLean. 2014. “Direct Visualization of CHIP-Mediated Degradation of Alpha-Synuclein In Vivo: Implications for PD Therapeutics.” PLoS ONE 9 (3): e92098. doi:10.1371/journal.pone.0092098. http://dx.doi.org/10.1371/journal.pone.0092098.
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Abstract: Parkinson's disease is a neurodegenerative disorder characterized by Lewy bodies, a pathological hallmark comprised mostly of aggregated alpha synuclein. Accumulating evidence demonstrates the association of smaller oligomeric aggregates to disease etiology and many therapeutic approaches are aimed at inhibiting and reducing the aggregation process. Molecular chaperones and co-chaperones play a key role in protein homeostasis and have potential as therapeutics to inhibit alpha synuclein associated toxicity. Here we use a gene therapy approach to evaluate the applicability of the Hsp70 co-chaperone CHIP (C-terminal Hsp70 interacting protein) as a therapeutic candidate and examine its direct effect on alpha synuclein aggregates in vivo. Utilizing a novel viral vector mediated rat model to directly detect alpha synuclein aggregates, we show that CHIP can mediate the degradation of alpha synuclein aggregates in vivo. However, our studies also reveal that CHIP may potentially degrade tyrosine hydroxylase which would compromise the applicability of CHIP as a therapeutic approach for Parkinson's disease.
Published Version: doi:10.1371/journal.pone.0092098
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963877/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12064493
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