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A comparison of changes in proteasomal subunit expression in the substantia nigra in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

Research output: Contribution to journalArticle

Salma Bukhatwa, Bai-Yun Zeng, Sarah Rose, Peter Jenner

Original languageEnglish
Pages (from-to)174 - 183
Number of pages10
JournalBrain Research
Volume1326
DOIs
Publication statusPublished - 22 Apr 2010

King's Authors

Abstract

Dysfunction of the ubiquitin-proteasome system (UPS) occurs in dopaminergic neurones in the SN in PD and it is associated with Lewy body formation. However, it remains unknown whether this is specific to PD or whether it also occurs in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) where nigral dopaminergic neurones also degenerate. In the present study, we investigated changes in the expression of proteasomal subunits in the SN in PD, MSA and PSP. Immunohistochemistry double staining showed that proteasome 205-alpha 4 and -alpha 6, and 20S-beta 3 and -beta Si subunits are colocalized with tyrosine hydroxylase (TH)-positive cells in the SN of control, PD, MSA and PSP brain. Semi-quantitative analysis showed a significant loss of 20S-alpha 4 and -alpha 6 subunits TH-positive cells in PD, MSA and PSP compared to control tissue. There was no change in the expression of 20S-beta 3 and -beta Si subunits in any of the disease states. The expression of PA700-Rpt5 subunits was not changed in PSP or PD but was significantly increased in MSA compared to control SN. PA700-Rpn10 subunit was not colocalized with TH within dopamine cells but was co-expressed with glial fibrillary acid protein (GFAP) positive astrocytes in the SN of all groups. PA28-alpha immunoreactivity was low in TH positive neurones in control tissue and quantification was not possible. Qualitative analysis suggested a decrease in PD and no immunoreactivity was detected in MSA or PSP. The results show that changes in proteasomal structure occur in the SN in PD, MSA and PSP and that these are similar in nature suggesting that dysfunction of UPS is not specific to PD or to Lewy body formation. (C) 2010 Elsevier BM. All rights reserved.

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