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Nature Medicine 7, 528 - 530 (2001)
doi:10.1038/87842

Polyglutamine and CBP: Fatal attraction?

Alexander McCampbell1 & Kenneth H. Fischbeck1

  1. Neurogenetics Branch National Institute of Neurological Disorders and Stroke Bethesda, Maryland, USA
    e-mail: kf@codon.nih.gov


The mutant proteins that cause polyglutamine disease bind CREB-binding protein (CBP), a key transcriptional co-activator for neuronal survival factors. This results in a loss of CBP-dependent transcription and may account for the neuronal degeneration associated with these diseases.


Eight hereditary neurodegenerative diseases are known to be caused by polyglutamine-repeat expansions1. The expansions make the mutant proteins toxic to neurons, possibly through abnormal interactions with polyglutamine tracts in other, normal proteins2.

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