Research article summary (published 8 Apr 2008):

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

Full 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.

Author information

Author/s: MacInnes, Nicholas (N); Iravani, Mahmoud M (MM); Perry, Elaine (E); Piggott, Margaret (M); Perry, Robert (R); Jenner, Peter (P); Ballard, Clive (C);

Affiliation: Wolfson Centre for Age-Related Disease, King's College London, London, UK. nicholas.macinnes(-atsign-)kcl.ac.uk

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm), published in Austria. (Language: eng)

Reference: 2008-Jun; vol 115 (issue 6) : pp 869-78

Dates: Created 2008/06/04; Completed 2008/10/03;

PMID: 18401540, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetylcholine - metabolism Acetylcysteine - analogs & derivatives; toxicity Aged Aged, 80 and over Animals Basal Nucleus of Meynert - drug effects; metabolism; pathology Cell Death - drug effects; physiology Cells, Cultured Cerebral Cortex - drug effects; metabolism; pathology Cholinergic Fibers - drug effects; metabolism; pathology Disease Models, Animal Dose-Response Relationship, Drug Enzyme Inhibitors - toxicity Female

Female Humans Lewy Bodies - drug effects; metabolism; pathology Lewy Body Disease - chemically induced; metabolism; pathology Male Nerve Degeneration - chemically induced; metabolism; pathology Nerve Tissue Proteins - metabolism Neural Pathways - drug effects; metabolism; pathology Oligopeptides - toxicity Proteasome Endopeptidase Complex - antagonists & inhibitors; metabolism Rats Rats, Sprague-Dawley Ubiquitin - drug effects; metabolism alpha-Synuclein - drug effects; metabolism

Associated Chemicals: Enzyme Inhibitors (0) ; Nerve Tissue Proteins (0) ; Oligopeptides (0) ; Ubiquitin (0) ; alpha-Synuclein (0) ; lactacystin (133343-34-7) ; epoxomicin (134381-21-8) ; Acetylcholine (51-84-3) ; Acetylcysteine (616-91-1) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)

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