Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Polyglutamine neurodegeneration: minding your Ps and Qs

Nature Medicine volume 9, pages 825–826 (2003)Cite this article

Expanded glutamine repeats cause brain degeneration associated with protein misfolding and aggregation. Two studies now look beyond the repeat, implicating the phosphatidylinositol-3-kinase (PI-3K)/Akt signaling pathway and 14-3-3 proteins in polyglutamine toxicity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Purkinje cells from 27-week-old mouse brains stained with ataxin-1 (green) and calbindin (red), a calcium-binding protein expressed in Purkinje cells.

Reprinted with permission from Elsevier Science

Figure 2: Beyond the glutamine repeat.

Reprinted with permission from Elsevier Science

References

  1. Taylor, J.P., Hardy, J. & Fischbeck, K.H. Toxic proteins in neurodegenerative disease. Science 296, 1991–1995 (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Emamian, E.S. et al. Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron 38, 375–387 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Chen, H.K. et al. Interaction of akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1. Cell 113, 457–468 (2003).

    Article  CAS  PubMed  Google Scholar 

  4. Orr, H.T. & Zoghbi, H.Y. SCA1 molecular genetics: a history of a 13 year collaboration against glutamines. Hum. Mol. Genet. 10, 2307–2311 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Fernandez-Funez, P. et al. Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 408, 101–106 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Bonini, N.M. Chaperoning brain degeneration. Proc. Natl. Acad. Sci. USA 99 (suppl. 4), 16407–16411 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hsu, A.L., Murphy, C.T. & Kenyon, C. Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300, 1142–1145 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Waelter, S. et al. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell 12, 1393–1407 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Humbert, S. et al. The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. Dev. Cell 2, 831–837 (2002).

    Article  CAS  PubMed  Google Scholar 

  10. Kawamoto, Y., Akiguchi, I., Nakamura, S. & Budka, H. Accumulation of 14-3-3 proteins in glial cytoplasmic inclusions in multiple system atrophy. Ann. Neurol. 52, 722–731 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Xu, J. et al. Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat. Med. 8, 600–606 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Hashiguchi, M., Sobue, K. & Paudel, H.K. 14-3-3zeta is an effector of tau protein phosphorylation. J. Biol. Chem. 275, 25247–25254 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Katsuno, M. et al. Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat. Med. 9, 768–773 (2003).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The author is in the Department of Neurology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, 52245, Iowa, USA

    Henry Paulson

Authors
  1. Henry Paulson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paulson, H. Polyglutamine neurodegeneration: minding your Ps and Qs. Nat Med 9, 825–826 (2003). https://doi.org/10.1038/nm0703-825

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0703-825

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing