The link between Huntington's disease and a protein known as ubiquitin may be greater than previously thought, according to a paper published online in Nature.
Huntington's disease is an inherited neurodegenerative disorder, characterized by the accumulation of protein fragments in affected neurons. These so-called inclusion bodies are often abnormally enriched with ubiquitin, suggesting that alterations in the metabolism of this protein might contribute to the disease. Using mass spectrometry, Ron R. Kopito and colleagues systematically analysed the brains of patients with Huntington's disease as well as two different mouse models of the disease. All of the brain samples contained an abundance of chains of polyubiquitin, establishing changes in the ubiquitin system as a consistent feature of Huntington's disease pathology.
Protein modification with polyubiquitin chains regulates many essential cellular processes - such as the cell cycle and DNA repair - so altered ubiquitin signalling is likely to have broad consequences for the function and survival of neurons. The authors propose that their technique might be used to achieve a deeper insight into the molecular basis of a variety of neurodegenerative diseases.
Ron R. Kopito (Stanford University, CA, USA)
(C) Nature press release.
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