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Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease

Duke, Dawn, Moran, L. B., Kalaitzakis, M. E., Deprez, M., Dexter, D. T., Pearce, R. K. B. and Graeber, M. B. (2006) Transcriptome analysis reveals link between proteasomal and mitochondrial pathways in Parkinson’s disease Neurogenetics, 7 (3). pp. 139-148.

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Abstract

There is growing evidence that dysfunction of the mitochondrial respiratory chain and failure of the cellular protein degradation machinery, specifically the ubiquitin–proteasome system, play an important role in the pathogenesis of Parkinson’s disease. We now show that the corresponding pathways of these two systems are linked at the transcriptomic level in Parkinsonian substantia nigra. We examined gene expression in medial and lateral substantia nigra (SN) as well as in frontal cortex using whole genome DNA oligonucleotide microarrays. In this study, we use a hypothesis-driven approach in analysing microarray data to describe the expression of mitochondrial and ubiquitin–proteasomal system (UPS) genes in Parkinson’s disease (PD). Although a number of genes showed up-regulation, we found an overall decrease in expression affecting the majority of mitochondrial and UPS sequences. The down-regulated genes include genes that encode subunits of complex I and the Parkinson’s-disease-linked UCHL1. The observed changes in expression were very similar for both medial and lateral SN and also affected the PD cerebral cortex. As revealed by “gene shaving” clustering analysis, there was a very significant correlation between the transcriptomic profiles of both systems including in control brains. Therefore, the mitochondria and the proteasome form a higher-order gene regulatory network that is severely perturbed in Parkinson’s disease. Our quantitative results also suggest that Parkinson’s disease is a disease of more than one cell class, i.e. that it goes beyond the catecholaminergic neuron and involves glia as well.

Item Type: Article
Divisions : Researcher Development Programme
Authors :
NameEmailORCID
Duke, DawnD.Duke@surrey.ac.ukUNSPECIFIED
Moran, L. B.UNSPECIFIEDUNSPECIFIED
Kalaitzakis, M. E.UNSPECIFIEDUNSPECIFIED
Deprez, M.UNSPECIFIEDUNSPECIFIED
Dexter, D. T.UNSPECIFIEDUNSPECIFIED
Pearce, R. K. B.UNSPECIFIEDUNSPECIFIED
Graeber, M. B.UNSPECIFIEDUNSPECIFIED
Date : July 2006
Identification Number : 10.1007/s10048-006-0033-5
Copyright Disclaimer : © Springer-Verlag 2006.
Uncontrolled Keywords : Alpha-synuclein; Gene shaving; Microarrays; Oxidative stress; Ubiquitin–proteasome system
Depositing User : Clive Harris
Date Deposited : 20 Jun 2017 10:58
Last Modified : 20 Jun 2017 10:58
URI: http://epubs.surrey.ac.uk/id/eprint/841434

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