University of Hertfordshire

  • Nicholas MacInnes
  • Mahmoud M. Iravani
  • Elaine Perry
  • Margaret Piggott
  • Robert Perry
  • Peter Jenner
  • Clive Ballard
View graph of relations
Original languageEnglish
Pages (from-to)869-878
Number of pages10
JournalJournal of Neural Transmission
Volume115
Issue6
DOIs
Publication statusPublished - Jun 2008

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.

ID: 735109