Research

Proteome analysis of human substantia nigra in Parkinson's disease

Cornelius J Werner^1,2 , Roland Heyny-von Haussen³ , Gerhard Mall³ and Sabine Wolf⁴

¹  Department of Neurology, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany

²  Institute of Neuroscience and Biophysics – Department of Medicine, Research Centre Juelich, 52425 Juelich, Germany

³  Institute of Pathology, Klinikum Darmstadt, Grafenstrasse 9, 64283 Darmstadt, Germany

⁴  Clemens-Schöpf-Institute for Organic Chemistry and Biochemistry, Technical University Darmstadt, Petersenstrasse 22, 64285 Darmstadt, Germany

author email corresponding author email

Proteome Science 2008, 6:8doi:10.1186/1477-5956-6-8

Published:	14 February 2008

Abstract

Background

Parkinson's disease (PD) is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra.

Results

The gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin) and glutathione-related redox metabolism (GST M3, GST P1, GST O1), including novel redox proteins (SH3BGRL). Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin), as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation), aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism). Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism) and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results.

Conclusion

Using an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many more proteins than previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease.