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. doi:10.1007/s00018-010-0483-7 ISSN 1420-682X.

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Abstract

The 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
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Presynaptic receptors, Glyoxalase, Glycosylation, Glucose -- Metabolism
Journal or Publication Title:	Cellular and Molecular Life Sciences
Publisher:	Springer
ISSN:	1420-682X
Official Date:	February 2011
Dates:	Date Event February 2011 Published
Volume:	Vol.68
Number:	No.4
Page Range:	pp. 721-733
DOI:	10.1007/s00018-010-0483-7
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Deutsche Forschungsgemeinschaft (DFG), Germany. Bundesministerium für Gesundheit [Ministry of Health]
Grant number:	GI342/1-1 (DFG), GI342/3-1 (DFG), AU96/10-1 (DFG), 01GS0472 (MoH), 01GS08138 (MoH), 0315584A (MoH)

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