Methylglyoxal, the dark side of glycolysis

Handle URI:
http://hdl.handle.net/10754/344332
Title:
Methylglyoxal, the dark side of glycolysis
Authors:
Allaman, Igor; Bélanger, Mireille; Magistretti, Pierre J. ( 0000-0002-6678-320X )
Abstract:
Glucose is the main energy substrate for the brain. There is now extensive evidence indicating that the metabolic profile of neural cells with regard to glucose utilization and glycolysis rate is not homogenous, with a marked propensity for glycolytic glucose processing in astrocytes compared to neurons. Methylglyoxal, a highly reactive dicarbonyl compound, is inevitably formed as a by-product of glycolysis. Methylglyoxal is a major cell-permeant precursor of advanced glycation end-products (AGEs), which are associated with several pathologies including diabetes, aging and neurodegenerative diseases. In normal situations, cells are protected against methylglyoxal toxicity by different mechanisms and in particular the glyoxalase system, which represents the most important pathway for the detoxification of methylglyoxal. While the neurotoxic effects of methylglyoxal and AGEs are well characterized, our understanding the glyoxalase system in the brain is more scattered. Considering the high energy requirements (i.e., glucose) of the brain, one should expect that the cerebral glyoxalase system is adequately fitted to handle methylglyoxal toxicity. This review focuses on our actual knowledge on the cellular aspects of the glyoxalase system in brain cells, in particular with regard to its activity in astrocytes and neurons. A main emerging concept is that these two neural cell types have different and energetically adapted glyoxalase defense mechanisms which may serve as protective mechanism against methylglyoxal-induced cellular damage.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Allaman I, Bélanger M and Magistretti PJ (2015) Methylglyoxal, the dark side of glycolysis. Front. Neurosci. 9:23. doi: 10.3389/fnins.2015.00023
Publisher:
Frontiers Media S.A.
Journal:
Frontiers in Neuroscience
Issue Date:
9-Feb-2015
DOI:
10.3389/fnins.2015.00023
PubMed ID:
25709564
PubMed Central ID:
PMC4321437
Type:
Article
ISSN:
1662-453X
Sponsors:
This work was supported by grants from Swiss National Science Foundation (FNRS) (no. 310030B-148169/1), from the NCCR Synapsy and from the Biaggi and Panacée Foundations to Pierre J. Magistretti.
Additional Links:
http://www.frontiersin.org/Neuroenergetics%2c_Nutrition_and_Brain_Health/10.3389/fnins.2015.00023/abstract
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorAllaman, Igoren
dc.contributor.authorBélanger, Mireilleen
dc.contributor.authorMagistretti, Pierre J.en
dc.date.accessioned2015-02-10T07:57:52Z-
dc.date.available2015-02-10T07:57:52Z-
dc.date.issued2015-02-09en
dc.identifier.citationAllaman I, Bélanger M and Magistretti PJ (2015) Methylglyoxal, the dark side of glycolysis. Front. Neurosci. 9:23. doi: 10.3389/fnins.2015.00023en
dc.identifier.issn1662-453Xen
dc.identifier.pmid25709564en
dc.identifier.doi10.3389/fnins.2015.00023en
dc.identifier.urihttp://hdl.handle.net/10754/344332en
dc.description.abstractGlucose is the main energy substrate for the brain. There is now extensive evidence indicating that the metabolic profile of neural cells with regard to glucose utilization and glycolysis rate is not homogenous, with a marked propensity for glycolytic glucose processing in astrocytes compared to neurons. Methylglyoxal, a highly reactive dicarbonyl compound, is inevitably formed as a by-product of glycolysis. Methylglyoxal is a major cell-permeant precursor of advanced glycation end-products (AGEs), which are associated with several pathologies including diabetes, aging and neurodegenerative diseases. In normal situations, cells are protected against methylglyoxal toxicity by different mechanisms and in particular the glyoxalase system, which represents the most important pathway for the detoxification of methylglyoxal. While the neurotoxic effects of methylglyoxal and AGEs are well characterized, our understanding the glyoxalase system in the brain is more scattered. Considering the high energy requirements (i.e., glucose) of the brain, one should expect that the cerebral glyoxalase system is adequately fitted to handle methylglyoxal toxicity. This review focuses on our actual knowledge on the cellular aspects of the glyoxalase system in brain cells, in particular with regard to its activity in astrocytes and neurons. A main emerging concept is that these two neural cell types have different and energetically adapted glyoxalase defense mechanisms which may serve as protective mechanism against methylglyoxal-induced cellular damage.en
dc.description.sponsorshipThis work was supported by grants from Swiss National Science Foundation (FNRS) (no. 310030B-148169/1), from the NCCR Synapsy and from the Biaggi and Panacée Foundations to Pierre J. Magistretti.en
dc.language.isoenen
dc.publisherFrontiers Media S.A.en
dc.relation.urlhttp://www.frontiersin.org/Neuroenergetics%2c_Nutrition_and_Brain_Health/10.3389/fnins.2015.00023/abstracten
dc.rights© 2015 Allaman, Bélanger and Magistretti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectmethylglyoxalen
dc.subjectneuronen
dc.subjectastrocyteen
dc.subjecttriosephosphateen
dc.subjectadvanced-glycation end-products (AGEs)en
dc.subjectglutathioneen
dc.titleMethylglyoxal, the dark side of glycolysisen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalFrontiers in Neuroscienceen
dc.identifier.pmcidPMC4321437en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerlanden
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorMagistretti, Pierre J.en

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