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Proteasomal abnormalities in cortical Lewy body disease and the impact of proteasomal inhibition within cortical and cholinergic systems

Lookup NU author(s): Emeritus Professor Elaine Perry, Dr Margaret Piggott, Emeritus Professor Robert Perry, Dr Clive Ballard

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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 α-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 α-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. © 2008 Springer-Verlag.

Publication metadata

Author(s): MacInnes N, Iravani MM, Perry E, Piggott M, Perry R, Jenner P, Ballard C

Publication type: Article

Publication status: Published

Journal: Journal of Neural Transmission

Year: 2008

Volume: 115

Issue: 6

Pages: 869-878

ISSN (print): 0300-9564

ISSN (electronic): 1435-1463

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00702-008-0027-6

DOI: 10.1007/s00702-008-0027-6

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