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Nature Medicine 9, 825 - 826 (2003)
doi:10.1038/nm0703-825

Polyglutamine neurodegeneration: minding your Ps and Qs

Henry Paulson1

  1. The author is in the Department of Neurology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52245, USA. e-mail: henry-paulson@uiowa.edu


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.


Most neurodegenerative disorders that afflict humans are caused, in part, by abnormal protein accumulation and aggregation1. Among these disorders, the polyglutamine diseases are particularly intriguing: at least nine inherited diseases result from CAG repeat mutations that encode abnormally long polyglutamine domains in otherwise unrelated disease proteins.

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