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    Neurosci Lett. 2009 Sep 4;460(3):205-8. Epub 2009 Jun 7.

    Immunoreactivity to Lys63-linked polyubiquitin is a feature of neurodegeneration.

    Paine S, Bedford L, Thorpe JR, Mayer RJ, Cavey JR, Bajaj N, Sheppard PW, Lowe J, Layfield R.

    Source

    School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. simon.paine@nottingham.ac.uk

    Abstract

    The major human neurodegenerative diseases are characterised by ubiquitin-positive intraneuronal inclusions, however the precise nature of the ubiquitin modifications in these structures is unclear. Using a monoclonal antibody specific for Lys63-linked polyubiquitin we have performed the first immunohistochemical analysis of linkage-specific ubiquitination in vivo associated with neurodegeneration. Immunoreactivity was detected within the pathological lesions of Alzheimer's, Huntington's and Parkinson's disease brains, although staining of Lewy bodies in the substantia nigra in Parkinson's disease was rare, indicating a selective involvement of Lys63-linked polyubiquitin in inclusion biogenesis in this disorder. Immunoreactivity was also a feature in neurons of proteasome-depleted mice, suggesting a proteasomal contribution to the degradation of Lys63-linked polyubiquitinated proteins in vivo.

    PMID:
    19500650
    [PubMed - indexed for MEDLINE]

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