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J Neural Transm (Vienna). 2004 Dec;111(12):1543-73. Epub 2004 Sep 30.

Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes.

Author information

1
Institute of Clinical Neurochemistry and National Parkinson Foundation Centre of Excellence Laboratories, Clinic and Policlinic for Psychiatry and Psychotherapy, University of Würzburg, Germany.

Abstract

Gene expression profiling of human substantia nigra pars compacta (SNpc) from Parkinson's disease (PD) patients, was examined employing high density microarrays. We identified alterations in the expression of 137 genes, with 68 down regulated and 69 up regulated. The down regulated genes belong to signal transduction, protein degradation (e.g. ubiquitin-proteasome subunits), dopaminergic transmission/metabolism, ion transport, protein modification/phosphorylation and energy pathways/glycolysis functional classes. Up-regulated genes, clustered mainly in biological processes involving cell adhesion/cytoskeleton, extracellular matrix components, cell cycle, protein modification/phosphorylation, protein metabolism, transcription and inflammation/stress (e.g. key iron and oxygen sensor EGLN1). One major finding in the present study is the particular decreased expression of SKP1A, a member of the SCF (E3) ligase complex specifically in the substantia nigra (SN) of sporadic parkinsonian patients, which may lead to a wide impairment in the function of an entire repertoire of proteins subjected to regulatory ubiquitination. These findings reveal novel players in the neurodegenerative scenario and provide potential targets for the development of novel drug compounds.

PMID:
15455214
DOI:
10.1007/s00702-004-0212-1
[Indexed for MEDLINE]

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