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Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits.

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  • معلومة اضافية
    • NAICS/Industry Codes:
      112990 All Other Animal Production
    • Abstract:
      Regulated protein degradation by the proteasome plays an essential role in the enhancement and suppression of signaling pathways in the nervous system. Proteasome-associated factors are pivotal in ensuring appropriate protein degradation, and we have previously demonstrated that alterations in one of these factors, the proteasomal deubiquitinating enzyme ubiquitin-specific protease 14 (Usp14), can lead to proteasome dysfunction and neurological disease. Recent studies in cell culture have shown that Usp14 can also stabilize the expression of over-expressed, disease-associated proteins such as tau and ataxin-3. Using Usp14-deficient ax¹ mice, we investigated if loss of Usp14 results in decreased levels of endogenous tau and ataxin-3 in the nervous system of mice. Although loss of Usp14 did not alter the overall neuronal levels of tau and ataxin-3, we found increased levels of phosphorylated tau that correlated with the onset of axonal varicosities in the Usp14-deficient mice. These changes in tau phosphorylation were accompanied by increased levels of activated phospho-Akt, phosphorylated MAPKs, and inactivated phospho-GSK3β. However, genetic ablation of tau did not alter any of the neurological deficits in the Usp14-deficient mice, demonstrating that increased levels of phosphorylated tau do not necessarily lead to neurological disease. Due to the widespread activation of intracellular signaling pathways induced by the loss of Usp14, a better understanding of the cellular pathways regulated by the proteasome is required before effective proteasomal-based therapies can be used to treat chronic neurological diseases. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1Department of Neurobiology, Civitan International Research Center, University of Alabama, Birmingham, Birmingham, Alabama, United States of America
      2Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America
      3Department of Developmental Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America
      4Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
      5Department of Anesthesiology, University of Rochester, Rochester, New York, United States of America
      6Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
    • ISSN:
      1932-6203
    • Accession Number:
      10.1371/journal.pone.0047884
    • Accession Number:
      83524001
  • Citations
    • ABNT:
      JIN, Y. N. et al. Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits. PLoS ONE, [s. l.], v. 7, n. 10, p. 1–10, 2012. DOI 10.1371/journal.pone.0047884. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=83524001&custid=s8280428. Acesso em: 10 ago. 2020.
    • AMA:
      Jin YN, Ping-Chung Chen, Watson JA, et al. Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits. PLoS ONE. 2012;7(10):1-10. doi:10.1371/journal.pone.0047884
    • APA:
      Jin, Y. N., Ping-Chung Chen, Watson, J. A., Walters, B. J., Phillips, S. E., Green, K., Schmidt, R., Wilson, J. A., Johnson, G. V., Roberson, E. D., Dobrunz, L. E., & Wilson, S. M. (2012). Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits. PLoS ONE, 7(10), 1–10. https://doi.org/10.1371/journal.pone.0047884
    • Chicago/Turabian: Author-Date:
      Jin, Youngnam N., Ping-Chung Chen, Jennifer A. Watson, Brandon J. Walters, Scott E. Phillips, Karen Green, Robert Schmidt, et al. 2012. “Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits.” PLoS ONE 7 (10): 1–10. doi:10.1371/journal.pone.0047884.
    • Harvard:
      Jin, Y. N. et al. (2012) ‘Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits’, PLoS ONE, 7(10), pp. 1–10. doi: 10.1371/journal.pone.0047884.
    • Harvard: Australian:
      Jin, YN, Ping-Chung Chen, Watson, JA, Walters, BJ, Phillips, SE, Green, K, Schmidt, R, Wilson, JA, Johnson, GV, Roberson, ED, Dobrunz, LE & Wilson, SM 2012, ‘Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits’, PLoS ONE, vol. 7, no. 10, pp. 1–10, viewed 10 August 2020, .
    • MLA:
      Jin, Youngnam N., et al. “Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits.” PLoS ONE, vol. 7, no. 10, Oct. 2012, pp. 1–10. EBSCOhost, doi:10.1371/journal.pone.0047884.
    • Chicago/Turabian: Humanities:
      Jin, Youngnam N., Ping-Chung Chen, Jennifer A. Watson, Brandon J. Walters, Scott E. Phillips, Karen Green, Robert Schmidt, et al. “Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits.” PLoS ONE 7, no. 10 (October 2012): 1–10. doi:10.1371/journal.pone.0047884.
    • Vancouver/ICMJE:
      Jin YN, Ping-Chung Chen, Watson JA, Walters BJ, Phillips SE, Green K, et al. Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits. PLoS ONE [Internet]. 2012 Oct [cited 2020 Aug 10];7(10):1–10. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=83524001&custid=s8280428