Powered by OpenAIRE graph
Found an issue? Give us feedback
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ NARCISarrow_drop_down
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
Europe PubMed Central
Other literature type . 2015
Data sources: PubMed Central
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
Molecular Medicine
Article . 2015 . Peer-reviewed
License: CC BY
versions View all 7 versions
addClaim

This Research product is the result of merged Research products in OpenAIRE.

You have already added 0 works in your ORCID record related to the merged Research product.

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Authors: Snijder, Pauline M.; Baratashvili, Madina; Grzeschik, Nicola A.; Leuvenink, Henri G. D.; Kuijpers, Lucas; Huitema, Sippie; Schaap, Onno; +12 Authors

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Abstract

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ataxin-3 (ATXN3) gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3. Here we show that overexpression of cystathionine.-lyase, a central enzyme in cysteine metabolism, is protective in a Drosophila model for SCA3. SCA3 flies show eye degeneration, increased oxidative stress, insoluble protein aggregates, reduced levels of protein persulfidation and increased activation of the innate immune response. Overexpression of Drosophila cystathionine.-lyase restores protein persulfidation, decreases oxidative stress, dampens the immune response and improves SCA3-associated tissue degeneration. Levels of insoluble protein aggregates are not altered; therefore, the data implicate a modifying role of cystathionine.-lyase in ameliorating the downstream consequence of protein aggregation leading to protection against SCA3-induced tissue degeneration. The cystathionine.-lyase expression is decreased in affected brain tissue of SCA3 patients, suggesting that enhancers of cystathionine.-lyase expression or activity are attractive candidates for future therapies.

Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3402]

Countries
Serbia, Germany, Netherlands
Subjects by Vocabulary

Microsoft Academic Graph classification: Inflammation Biology Protein aggregation medicine.disease_cause medicine Innate immune system medicine.disease Cystathionine beta synthase Cell biology Tissue Degeneration Biochemistry biology.protein Spinocerebellar ataxia medicine.symptom Trinucleotide repeat expansion Oxidative stress

Dewey Decimal Classification: ddc:540

Keywords

RENAL ISCHEMIA/REPERFUSION, INDUCED INFLAMMATION, BETA-SYNTHASE, S-SULFHYDRATION, Genetics, OXIDATIVE STRESS, Molecular Biology, Genetics (clinical), LIFE-SPAN, SODIUM THIOSULFATE, Articles, Naturwissenschaftliche Fakultät, HYDROGEN-SULFIDE PROTECTS, DROSOPHILA-MELANOGASTER, Molecular Medicine, MEDIATED NEURODEGENERATION

72 references, page 1 of 8

1. Zoghbi HY, Orr HT. (2000) Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci. 23:217-47.

2. Hageman J, et al. (2010) A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol. Cell. 37:355-69.

3. Dueñas AM, Goold R, Giunti P. (2006) Molecular pathogenesis of spinocerebellar ataxias. Brain. 129:1357-70.

4. Frake RA, Ricketts T, Menzies FM, Rubinsztein DC. (2015) Autophagy and neurodegeneration. J. Clin. Invest. 125:65-74. [OpenAIRE]

5. Lee S, Lim H, Masliah E, Lee H. (2011) Protein aggregate spreading in neurodegenerative diseases: problems and perspectives. Neurosci. Res. 70:339-48.

6. Takahashi T, Katada S, Onodera O. (2010) Polyglutamine diseases: where does toxicity come from? what is toxicity? where are we going? J. Mol. Cell Biol. 2:180-91.

7. Seidel K, et al. (2012) Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type 3 (SCA3). Neuropathol. Appl. Neurobiol. 38:548-58.

8. Kabil O, Banerjee R. (2014) Enzymology of H2S biogenesis, decay and signaling. Antioxid. Redox Signal. 20:770-82.

9. Kabil O, Motl N, Banerjee R. (2014) H2S and its role in redox signaling. Biochim. Biophys. Acta. 1844:1355-66.

10. Kabil H, Kabil O, Banerjee R, Harshman LG, Pletcher SD. (2011) Increased transsulfuration mediates longevity and dietary restriction in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 108:16831-6.

  • BIP!
    Impact byBIP!
    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    40
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
    OpenAIRE UsageCounts
    Usage byUsageCounts
    visibility views 136
    download downloads 229
  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    40
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
    Powered byBIP!BIP!
  • 136
    views
    229
    downloads
    Powered byOpenAIRE UsageCounts
Powered by OpenAIRE graph
Found an issue? Give us feedback
visibility
download
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
OpenAIRE UsageCountsDownloads provided by UsageCounts
40
Top 10%
Average
Top 10%
136
229
Green
gold