The interaction between RE1-silencing transcription factor (REST) and heat shock protein 90 as new therapeutic target against Huntington's disease

PloS One
Raúl Orozco-DíazJosé Tapia-Ramírez

Abstract

The wild type huntingtin protein (Htt), supports the production of brain-derived neurotrophic factor (BDNF), a survival factor for striatal neurons, through cytoplasmic sequestering of RE-1silencing transcription factor (REST). In Huntington´s Disease an inherited degenerative disease, caused by a CAG expansion in the 5´coding region of the gene, the mutant huntingtin protein (mHtt), causes that REST enters pathologically into the nucleus of cells, resulting in the repression of neuronal genes including BDNF, resulting in the progressive neuronal death. It has been reported that Htt associates with Hsp90 and this interaction is involved in regulation of huntingtin aggregation. Discovering mechanisms to reduce the cellular levels of mutant huntingtin and REST provide promising strategies for treating Huntington disease. Here, we use the yeast two-hybrid system to show that N-terminus or REST interacts with the heat shock protein 90 (Hsp90) and identifies REST as an Hsp90 Client Protein. To assess the effects of Hsp90 we used antisense oligonucleotide, and evaluated the levels mHtt and REST levels. Our results show that direct knockdown of endogenous Hsp90 significantly reduces the levels of REST and mutant Huntingtin, decreased ...Continue Reading

References

Sep 1, 1988·Journal of Neuropathology and Experimental Neurology·S M de la MonteE P Richardson
Aug 30, 2003·Nature Genetics·Leslie Michels Thompson
May 25, 2004·Expert Opinion on Emerging Drugs·William A Denny
Jun 22, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Stefanie J OttoGail Mandel
Jan 9, 2010·Journal of Medicinal Chemistry·Marco A BiamonteWen-Cherng Lee
Jun 8, 2010·Molecular Neurodegeneration·Wenjie LuoGabriela Chiosis
Dec 24, 2010·PloS One·Myriam RavacheYvon Trottier
Aug 13, 2011·The Journal of Biological Chemistry·Moumita Datta, Nitai P Bhattacharyya
Nov 30, 2011·The Journal of Biological Chemistry·Barbara BaldoKlemens Kaupmann
Nov 14, 2012·Journal of Neurochemistry·Chiara SoldatiNoel J Buckley
Feb 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Carla NascaFerdinando Nicoletti
Apr 10, 2013·Epigenomics·Richard G Hunter, Bruce S McEwen
Dec 11, 2013·Bioinformatics and Biology Insights·Jun-Ichi SatohYoji Yamamoto
Mar 29, 2014·Nature·Tao LuBruce A Yankner
Apr 25, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Naoki KanekoR Suzanne Zukin
Mar 10, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Katelin P PattersonTallie Z Baram
May 20, 2017·Journal of Cellular and Molecular Medicine·Guo-Lin ChenGregory M Miller
Feb 8, 2018·Annual Review of Pathology·Madeline M Farley, Trent A Watkins
Jan 27, 2019·Neuroscience Letters·Miwako KawamuraNobutaka Hattori
Apr 21, 2019·Frontiers in Neuroendocrinology·Myrthe Mampay, Graham K Sheridan

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Citations

Oct 12, 2019·International Journal of Molecular Sciences·Anastasiia BohushAnna Filipek
Jan 8, 2020·International Journal of Molecular Sciences·Jose M Garcia-ManteigaJacopo Meldolesi
Aug 24, 2021·Frontiers in Cellular Neuroscience·Xiaoyu Dong, Shuyan Cong

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Datasets Mentioned

BETA
AB133491

Methods Mentioned

BETA
immunoprecipitation
Two-hybrid
pull-down
light microscopy
Antisense oligonucleotides
ELISA
double hybrid
pull down
transfection
confocal microscopy

Software Mentioned

GraphPad
GraphPad Prims
Image StudioTM Lite
BLAST

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