TY  - JOUR
A1  - Kurz, Alexander
A1  - Rabbani, Naila
A1  - Walter, Michael
A1  - Bonin, Michael
A1  - Thornalley, Paul
A1  - Auburger, Georg
A1  - Gispert, Suzana
T1  - Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress
T2  - Cellular and molecular life sciences
N2  - 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 alpha-synuclein ablation. We propose that wild-type alpha-synuclein modulates brain glucose metabolism.
KW  - Alpha-synuclein deficiency
KW  - Transcriptome microarray
KW  - Glyoxalase I
KW  - Advanced glycation endproducts
KW  - Glucose metabolism
Y1  - 2010
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/33421
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-334218
SN  - 1420-682X
SN  - 1420-9071
N1  - Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
VL  - 68
IS  - 4
SP  - 721
EP  - 733
PB  - Springer
CY  - Basel
ER  -