Downregulation of the Repressor Element 1-Silencing Transcription Factor (REST) Is Associated with Akt-mTOR and Wnt-β-Catenin Signaling in Prion Diseases Models

Frontiers in Molecular Neuroscience
Zhi-Qi SongDeming Zhao

Abstract

Prion diseases are a group of infectious diseases characterized by multiple neuropathological changes, yet the mechanisms that preserve function and protect against prion-associated neurodegeneration are still unclear. We previously reported that the repressor element 1-silencing transcription factor (REST) alleviates neurotoxic prion peptide (PrP106-126)-induced toxicity in primary neurons. Here we confirmed the findings of the in vitro model in 263K infected hamsters, an in vivo model of prion diseases and further showed the relationships between REST and related signaling pathways. REST was depleted from the nucleus in prion infected brains and taken up by autophagosomes in the cytoplasm, co-localizing with LC3-II. Importantly, downregulation of the Akt-mTOR and at least partially inactivation of LRP6-Wnt-β-catenin signaling pathways correlated with the decreased levels of REST in vivo in the brain of 263K-infected hamsters and in vitro in PrP106-126-treated primary neurons. Overexpression of REST in primary cortical neurons alleviated PrP106-126 peptide-induced neuronal oxidative stress, mitochondrial damage and partly inhibition of the LRP6-Wnt-β-catenin and Akt-mTOR signaling. Based on our findings, a model of REST-mediat...Continue Reading

References

Jan 1, 1991·Acta Neuropathologica·J W BoellaardH Diringer
Jan 1, 1995·Micron : the International Research and Review Journal for Microscopy·M JeffreyC M Goodsir
Apr 1, 1994·Experimental Cell Research·R BertrandY Pommier
Oct 21, 1998·The Journal of General Virology·D C Bolton
Nov 11, 1999·Oncogene·M S Sheikh, A J Fornace
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·P Cohen, S Frame
Oct 25, 2003·Biochemical and Biophysical Research Communications·Shigeki NishiharaToshihiko Ogura
Aug 18, 2004·Genes & Development·Nissim Hay, Nahum Sonenberg
Aug 25, 2004·The International Journal of Biochemistry & Cell Biology·Pawel P LiberskiPaul Brown
Jan 24, 2007·Nature Genetics·Xi C HeLinheng Li
Oct 6, 2007·Journal of Neuropathology and Experimental Neurology·Charleen T ChuKelly L Jordan-Sciutto
Apr 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Laurence AbramiF Gisou van der Goot
Aug 10, 2010·Acta Neuropathologica·Jonathan D F Wadsworth, John Collinge
Oct 5, 2010·Trends in Molecular Medicine·Claudio Soto, Nikunj Satani
Mar 8, 2011·The Biochemical Journal·Hwajin JungEek-hoon Jho
Aug 27, 2011·Journal of Cell Science·Romana TomasoniRosalba D'Alessandro
Oct 20, 2011·Journal of Cell Science·Mien-Chie Hung, Wolfgang Link
Nov 16, 2012·Nature Reviews. Molecular Cell Biology·Christof Niehrs
Feb 20, 2014·Journal of Molecular Cell Biology·Nibaldo C Inestrosa, Lorena Varela-Nallar
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Mitsugu Shimobayashi, Michael N Hall
Mar 19, 2014·CNS Neuroscience & Therapeutics·Zhi-Qi SongDe-Ming Zhao
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
Sep 23, 2014·Cell and Tissue Research·Nibaldo C Inestrosa, Lorena Varela-Nallar
Dec 7, 2014·Journal of Molecular Neuroscience : MN·Zhiqi SongLifeng Yang

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Citations

Jan 12, 2019·Journal of Neuroscience Research·Silvia VanniGiuseppe Legname
Aug 3, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Tomoko SogaIshwar S Parhar

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Methods Mentioned

BETA
electrophoresis
transfection
fluorescence microscopy
glycosylation

Software Mentioned

SPSS
GraphPad Prism
Image J

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