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Neurodegeneration

A question of balance

Nature volume 452, pages 707–708 (2008)Cite this article

When a disease-associated gene is mutated, is the cellular activity of its protein product enhanced or reduced? For at least one neurodegenerative disease, spinocerebellar ataxia 1, the answer seems to be both.

Ten devastating neurodegenerative disorders, including Huntington's disease, that are caused by mutations in unrelated genes have one feature in common: in the disease gene, the CAG nucleotide triplet, which encodes the glutamine amino acid, is repeated many times. Consequently, the resulting protein contains a tract of glutamine residues, and disorders with this feature are known collectively as polyglutamine-repeat diseases1. But although the polyglutamine chain is toxic to cells, it is not in itself sufficient to cause human disease1,2,3. So what are the other molecular players, and how do they interact to bring about neurodegeneration? To address these questions, Lim et al.4 (page 713) extended the search for molecular partners of ataxin 1 (ATXN1), which when mutated is responsible for the polyglutamine disease spinocerebellar ataxia 1, and tested whether interactions of ATXN1 with these partners is altered in disease. They find that ATXN1 mutation is accompanied by alterations in the cellular levels of at least two distinct ATXN1-containing, disease-associated protein complexes.

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Figure 1: Protein interactions implicated in spinocerebellar ataxia 1.

References

  1. Orr, H. T. & Zoghbi, H. Y. Annu. Rev. Neurosci. 30, 575–621 (2007).

    Article  CAS  Google Scholar 

  2. Katsuno, M. et al. Exp. Neurol. 200, 8–18 (2006).

    Article  CAS  Google Scholar 

  3. Li, S. & Li, X.-J. Mol. Neurodegen. 1, 19 (2006).

    Article  Google Scholar 

  4. Lim, J. et al. Nature 452, 713–718 (2008).

    Article  CAS  ADS  Google Scholar 

  5. Bates, G. P., Mangiarini, L. & Davies, S. W. Brain Pathol. 8, 699–714 (1998).

    Article  CAS  Google Scholar 

  6. Lam, Y. C. et al. Cell 127, 1335–1347 (2006).

    Article  CAS  Google Scholar 

  7. Shao, J. & Diamond, M. I. Human Mol. Genet. 16, R115–R123 (2007).

    Article  CAS  Google Scholar 

  8. Zuccato, C. et al. J. Neurosci. 27, 6972–6983 (2007).

    Article  CAS  Google Scholar 

  9. Kaltenbach, L. S. et al. PLoS Genet. 3, e82 (2007).

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Leslie Michels Thompson is in the Departments of Psychiatry and Human Behavior, of Neurobiology and Behavior and of Biological Chemistry, University of California, Irvine, Gillespie 2121, Irvine, California 92696-4260, USA. lmthomps@uci.edu,

    Leslie Michels Thompson

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Thompson, L. A question of balance. Nature 452, 707–708 (2008). https://doi.org/10.1038/452707a

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