Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress
Kurz, Alexander, Rabbani, Naila, Walter, Michael, Bonin, Michael, Thornalley, Paul J., Auburger, Georg and Gispert, Suzana (2011) Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress. Cellular and Molecular Life Sciences, Vol.68 (No.4). pp. 721-733. ISSN 1420-682X Official URL: http://dx.doi.org/10.1007/s00018-010-0483-7 AbstractThe presynaptic protein alpha-synuclein has received much attention because its gain-of-function is associated with Parkinson’s disease. However, its physiological function is still poorly understood. We studied brain regions of knock-out mice at different ages with regard to consistent upregulations of the transcriptome and focused on glyoxalase I (GLO1). The microarray data were confirmed in qPCR, immunoblot, enzyme activity, and behavior analyses. GLO1 induction is a known protective cellular response to glucose stress, representing efforts to decrease toxic levels of methylglyoxal (MG), glyoxal and advanced glycation endproducts (AGEs). Mass spectrometry quantification demonstrated a ubiquitous increase in MG and fructosyl-lysine as consequences of glucose toxicity, and consistent enhancement of certain AGEs. Thus, GLO1 induction in KO brain seems insufficient to prevent AGE formation. In conclusion, the data demonstrate GLO1 expression and glycation damage to be induced by alphasynuclein ablation. We propose that wild-type alpha-synuclein modulates brain glucose metabolism. | Item Type: | Journal Article |
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| Subjects: | Q Science > QP Physiology |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI)
Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Presynaptic receptors, Glyoxalase, Glycosylation, Glucose -- Metabolism |
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| Journal or Publication Title: | Cellular and Molecular Life Sciences |
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| Publisher: | Springer |
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| ISSN: | 1420-682X |
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| Date: | February 2011 |
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| Volume: | Vol.68 |
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| Number: | No.4 |
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| Page Range: | pp. 721-733 |
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| Status: | Peer Reviewed |
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| Publication Status: | Published |
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| Access rights to Published version: | Open Access |
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| Funder: | Deutsche Forschungsgemeinschaft (DFG), Germany. Bundesministerium für Gesundheit [Ministry of Health] |
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| Grant number: | GI342/1-1 (DFG), GI342/3-1 (DFG), AU96/10-1 (DFG), 01GS0472 (MoH), 01GS08138 (MoH), 0315584A (MoH) |
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