dc.contributor.author | MacInnes, Nicholas | |
dc.contributor.author | Iravani, Mahmoud M. | |
dc.contributor.author | Perry, Elaine | |
dc.contributor.author | Piggott, Margaret | |
dc.contributor.author | Perry, Robert | |
dc.contributor.author | Jenner, Peter | |
dc.contributor.author | Ballard, Clive | |
dc.date.accessioned | 2013-01-11T12:59:07Z | |
dc.date.available | 2013-01-11T12:59:07Z | |
dc.date.issued | 2008-06 | |
dc.identifier.citation | MacInnes , N , Iravani , M M , Perry , E , Piggott , M , Perry , R , Jenner , P & Ballard , C 2008 , ' Proteasomal abnormalities in cortical Lewy body disease and the impact of proteasomal inhibition within cortical and cholinergic systems ' , Journal of Neural Transmission , vol. 115 , no. 6 , pp. 869-878 . https://doi.org/10.1007/s00702-008-0027-6 | |
dc.identifier.issn | 0300-9564 | |
dc.identifier.other | ORCID: /0000-0002-4905-9682/work/32997580 | |
dc.identifier.uri | http://hdl.handle.net/2299/9573 | |
dc.description.abstract | Dementia with Lewy bodies (DLB) accounts for 15-20% of the millions of people worldwide with dementia. In the current work we investigate the association between proteasome dysfunction and the development of cortical Lewy body pathology. Analysis of post-mortem cortical tissue indicated levels of the alpha-subunit of the 20S proteasome were significantly reduced in DLB cortex, but not Alzheimer's, in comparison to control and this reduction correlated with both the severity and duration of dementia. Application of proteasome inhibitors to rodent cortical primary neurones in vitro and by direct injection onto rodent cholinergic forebrain neurons in vivo gave rise to dose dependent neuronal death and in rodent cortex--marked cholinergic deficits accompanied by the accumulation of inclusions that stained positive for alpha-synuclein and ubiquitin. These findings suggest that proteasomal abnormalities are present within cortical Lewy body disease and the experimental inhibition of proteasomal function mirrors the neuropathological changes seen within the disorder. | en |
dc.format.extent | 10 | |
dc.format.extent | 467828 | |
dc.language.iso | eng | |
dc.relation.ispartof | Journal of Neural Transmission | |
dc.subject | dementia with Lewy bodies | |
dc.subject | ubiquitin-proteasome system | |
dc.subject | nucleus basalis magnocellularis | |
dc.subject | lactacystin | |
dc.subject | alpha-synuclein | |
dc.subject | ubiquitin | |
dc.subject | PARKINSONS-DISEASE | |
dc.subject | ALPHA-SYNUCLEIN | |
dc.subject | TYROSINE-HYDROXYLASE | |
dc.subject | SUBSTANTIA-NIGRA | |
dc.subject | CELL-DEATH | |
dc.subject | DEMENTIA | |
dc.subject | BODIES | |
dc.subject | NEURONS | |
dc.subject | PREVALENCE | |
dc.subject | INCLUSIONS | |
dc.title | Proteasomal abnormalities in cortical Lewy body disease and the impact of proteasomal inhibition within cortical and cholinergic systems | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Basic and Clinical Science Unit | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.description.status | Peer reviewed | |
rioxxterms.versionofrecord | 10.1007/s00702-008-0027-6 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |