Source:http://linkedlifedata.com/resource/pubmed/id/21360076
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2011-3-16
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| pubmed:abstractText |
Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS). OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions were uncommon and detected in only 11/32 (34%) of TDP-43-positive SALS spinal cord and 5/15 (33%) of FTLD-TDP. Western blot of lysates from FTLD-TDP frontal cortex and TDP-43-positive SALS spinal cord revealed decreased levels of OPTN protein compared to controls (p < 0.05), however, this correlated with decreased neuronal numbers in the brain. Large OPTN inclusions were not detected in FALS with SOD-1 and FUS mutation, respectively, or in FTLD-FUS cases. OPTN-positive inclusions were identified in a few Alzheimer's disease (AD) cases but did not co-localise with tau and TDP-43. Occasional striatal neurons contained granular cytoplasmic OPTN immunopositivity in Huntington's disease (HD) but were absent in spinocerebellar ataxia type 3. No OPTN inclusions were detected in FTLD-tau and ?-synucleinopathy. We conclude that OPTN inclusions are relatively rare and largely restricted to a minority of TDP-43 positive ALS and FTLD-TDP cases. Our results do not support the proposition that OPTN inclusions play a central role in the pathogenesis of ALS, FTLD or any other neurodegenerative disorder.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DAPI,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Histamine Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/OPTN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor TFIIIA,
http://linkedlifedata.com/resource/pubmed/chemical/Tubulin,
http://linkedlifedata.com/resource/pubmed/chemical/beta III-tubulin protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/protein TDP-43,
http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
1432-0533
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| pubmed:author |
pubmed-author:Al-SarrajSafaS,
pubmed-author:HortobágyiTiborT,
pubmed-author:KingAndrewA,
pubmed-author:NishimuraAgnes LAL,
pubmed-author:RogeljBorisB,
pubmed-author:SeelaarHarroH,
pubmed-author:ShawChristopher ECE,
pubmed-author:TroakesClaireC,
pubmed-author:VanceCarolineC,
pubmed-author:van SwietenJohn CJC
|
| pubmed:issnType |
Electronic
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| pubmed:volume |
121
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
519-27
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| pubmed:meshHeading |
pubmed-meshheading:21360076-Aged,
pubmed-meshheading:21360076-Aged, 80 and over,
pubmed-meshheading:21360076-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:21360076-Brain,
pubmed-meshheading:21360076-DNA-Binding Proteins,
pubmed-meshheading:21360076-Female,
pubmed-meshheading:21360076-Frontotemporal Lobar Degeneration,
pubmed-meshheading:21360076-Histamine Agonists,
pubmed-meshheading:21360076-Humans,
pubmed-meshheading:21360076-Indoles,
pubmed-meshheading:21360076-Male,
pubmed-meshheading:21360076-Middle Aged,
pubmed-meshheading:21360076-Mutation,
pubmed-meshheading:21360076-Nerve Tissue Proteins,
pubmed-meshheading:21360076-Neurons,
pubmed-meshheading:21360076-Spinal Cord,
pubmed-meshheading:21360076-Superoxide Dismutase,
pubmed-meshheading:21360076-Transcription Factor TFIIIA,
pubmed-meshheading:21360076-Tubulin
|
| pubmed:year |
2011
|
| pubmed:articleTitle |
Optineurin inclusions occur in a minority of TDP-43 positive ALS and FTLD-TDP cases and are rarely observed in other neurodegenerative disorders.
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| pubmed:affiliation |
Department of Clinical Neuroscience, King's College London, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, De Crespigny Park, London SE58AF, UK. tibor.hortobagyi@kcl.ac.uk
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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