Cover Picture: Proteomics – Clinical Applications 5/2008

Abstract

AbstractIn this issue of Proteomics – Clinical Applications you will find the following highlighted articles:Honorary HUPO membership for miRNAs possibilities with Parkinsons?Micro (mi) RNAs are non‐translated 19‐ to 24‐mers produced by the Dicer nuclease from longer RNA transcripts. Hybridization of the oligonucleotide to an mRNA carrying the complementary sequence results in suppression (silencing) of translation of the message. It has been proposed that hundreds of miRNAs regulate expression of about one third of all messages. Gillardon et al. started out looking for marker proteins for early indication of Parkinsons disease (PD) using a transgenic mouse model. Given the ubiquity of miRNAs, they also screened for changes in miRNAs using chip arrays. Applying 2‐D DIGE revealed ∼1000 spots per gel, 11 in the mutant background were significant. Animals over‐expressing mutant α‐synuclein had two mitochondrial enzymes strongly down‐regulated. These mRNA levels were also observed to decline as a function of age in wt animals. Looking at miRNA levels showed 39 species changed. The decline in production of miR‐132 may provide the desired marker.Gillardon, F. et al., Proteomics Clin. Appl. 2008, 2, 697–705.Bi‐sickle built for troubleBack in those dark days (the 1980's) before automated DNA sequencing, before protein sequencing by MS/MS, human hemoglobin was the preferred model for teaching first year medical students the links between molecular and classic genetics and gene function. HbA had been sequenced and there were many natural mutants. We didn't know the details of the sickling event then (you'd just wave your hands if some bright, alert student asked), and now, almost 30 years later, we're still working on it. Biondani et al. use a mouse model of human SCD and proteomic tools to explore the proteins involved. Besides HbS, they found that chaperones HSP27 and HSP70, peroxiredoxin‐II plus approximately 60 other proteins exhibited a significant change in expression levels. Functionally, they fell into five groups: membrane‐cytoskeleton, metabolic, ubiquitin‐proteasome, flotillin, and chaperones. A big step for man.Biondani, A. et al., Proteomics Clin. Appl. 2008, 2, 706–719.Mystery molecule unmasked: The role of TorsinATorsinA was first recognized as the DYT1 gene which causes primary torsion dystonia, a progressive neuromuscular movement disorder. The gene is an autosomal dominant, most frequently in Ashkenazi families. The mutation is a short deletion (δGAG). Similar symptoms appear when the wild‐type gene is over‐expressed. A transgenic mouse model of it has been constructed. In this article, Grundmann et al. explored the effects of gene over‐expression in mice and human cell lines using oligonucleotide arrays and Western blots, looking for coordinately regulated transcription and functional groups. They found 26 up‐regulated species, 10 of which could be assigned to a function, and 8 down‐regulated, 4 of which could be assigned. The functions included “behavior,” “development and function of the nervous system,” “cell morphology,” cellular development,” and “cellular growth and proliferation.” Three signaling pathways were involved: glutamate receptors, B‐cell receptors, and toll‐like receptors. DYT1 was linked to a number of neurodevelopmental networks.Grundmann, K. et al., Proteomics Clin. Appl. 2008, 2, 720–736.