title: Optineurin in Huntington's disease intranuclear inclusions.
abstract: Optineurin mutations cause adult-onset primary open-angle glaucoma and have been associated with some familial forms of amyotrophic lateral sclerosis (ALS). Optineurin is involved in many cellular processes and interacts with a variety of proteins, among them huntingtin (htt). Here we report that in Huntington's disease (HD) cortex, optineurin frequently occurs in neuronal intranuclear inclusions, and to a lesser extent, in inclusions in the neuropil and in perikarya. Most intranuclear optineurin-positive inclusions were co-labeled for ubiquitin, but they were only occasionally and more weakly co-labeled for htt. Optineurin-labeled neuropil and perikaryal inclusions were commonly co-labeled for ubiquitin and htt. Although these inclusions were common in cortex, they were rare in striatum. Our results show that in HD optineurin is present in intranuclear, neuropil and perikaryal inclusions. It is not clear whether this indicates a primary involvement in the disease process. In HD, the known interaction of htt and optineurin may suggest that a different process takes place as compared to other neurodegenerative disorders.
authors.affiliation: Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada. claudia.schwab@ubc.ca
authors.forename: Claudia
authors.initials: C
authors.lastname: Schwab
authors.forename: Sheng
authors.initials: S
authors.lastname: Yu
authors.forename: Edith G
authors.initials: EG
authors.lastname: McGeer
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology / Q000648:ultrastructure*; D018797:Cell Cycle Proteins; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology*; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D035582:Transcription Factor TFIIIA / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D009687:Nuclear Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; D025801:Ubiquitin; C051774:neurofilament protein H