title: Immunoreactivity to Lys63-linked polyubiquitin is a feature of neurodegeneration.
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.
authors.affiliation: School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. simon.paine@nottingham.ac.uk
authors.forename: Simon
authors.initials: S
authors.lastname: Paine
authors.forename: Lynn
authors.initials: L
authors.lastname: Bedford
authors.forename: Julian R
authors.initials: JR
authors.lastname: Thorpe
authors.forename: R John
authors.initials: RJ
authors.lastname: Mayer
authors.forename: James R
authors.initials: JR
authors.lastname: Cavey
authors.forename: Nin
authors.initials: N
authors.lastname: Bajaj
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sheppard
authors.forename: James
authors.initials: J
authors.lastname: Lowe
authors.forename: Robert
authors.initials: R
authors.lastname: Layfield
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism
chemical_list: D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D008239:Lysine