Neurotoxicity of methylglyoxal and 3-deoxyglucosone on cultured cortical neurons: Synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases

Kikuchi, Seiji; Shinpo, Kazuyoshi; Moriwaka, Fumio; Makita, Zenji; Miyata, Toshio; Tashiro, Kunio

doi:10.1002/(sici)1097-4547(19990715)57:2<280::aid-jnr14>3.0.co;2-u

Cited by 129 publications

(25 citation statements)

References 36 publications

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“…It is homologous to the hydroxyacetylglutathione hydrolase (HAGH), which catalyses the detoxification of methylglyoxal to lactic acid and reduced gluthatione. Interestingly, methyolglyoxal is reported to be neurotoxic and is found in coffee and alcoholic beverages, which might explain their precipitating effect of attacks in PNKD [Kikuchi et al 1999;Nagao et al 1986]. Recently, Bruno and coworkers [2007] concluded, that PNKD should strictly be defined based on age at onset and ability to precipitate attacks by caffeine and alcohol.…”

Section: Geneticsmentioning

confidence: 99%

Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Unterberger

Trinka

2008

Ther Adv Neurol Disord

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Paroxysmal dyskinesias (PDs) are a rare group of hyperkinetic movement disorders mainly characterized by their episodic nature. Neurological examination may be entirely normal between the attacks. Three main types of PDs can be distinguished based on their precipitating events -(i) paroxysmal kinesigenic dyskinesias (PKD), (ii) paroxysmal non-kinesigenic dyskinesias (PNKD) and (iii) paroxysmal exercise-induced (exertion-induced) dyskinesias (PED). The diagnosis of PDs is based on their clinical presentation and precipitating events. Substantial progress has been made in the field of genetics and PDs. Treatment options mainly include anticonvulsants and benefit of treatment is depending on the type of PD. Most important differential diagnosis are non-epileptic psychogenic, non-epileptic organic and epileptic attack disorders, especially nocturnal frontal lobe epilepsy.

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Section: Geneticsmentioning

confidence: 99%

Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Unterberger

Trinka

2008

Ther Adv Neurol Disord

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“…It has been reported that 3DG is related to diabetic microangiopathy, 5) inhibits cell proliferation, 10) and induces apoptosis in cells. 11,12) 3,4-Dideoxyosone-3-ene (3,4DGE) and 5-hydroxymethylfurfral (HMF) as intermediates were formed from 3DG by dehydration. The intermediates are known as cytotoxic substances.…”

Section: Formation Of -Dicarbonylsmentioning

confidence: 99%

Identification and Determination of α-Dicarbonyl Compounds Formed in the Degradation of Sugars

Usui

Yanagisawa

Ohguchi

et al. 2007

Bioscience, Biotechnology, and Biochemistry

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“…which was associated with oxidative stress leading to apoptosis (Kikuchi et al, 1999;Di Loreto et al, 2008;Chen et al, 2010).…”

mentioning

confidence: 99%

Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection

Bélanger

Yang²,

Petit³

et al. 2011

J. Neurosci.

106

131

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The glyoxalase system is the most important pathway for the detoxification of methylglyoxal (MG), a highly reactive dicarbonyl compound mainly formed as a by-product of glycolysis. MG is a major precursor of advanced glycation end products (AGEs), which are associated with several neurodegenerative disorders. Although the neurotoxic effects of MG and AGEs are well characterized, little is known about the glyoxalase system in the brain, in particular with regards to its activity in different neural cell types. Results of the present study reveal that both enzymes composing the glyoxalase system [glyoxalase-1 (Glo-1) and Glo-2] were highly expressed in primary mouse astrocytes compared with neurons, which translated into higher enzymatic activity rates in astrocytes (9.9-and 2.5-fold, respectively). The presence of a highly efficient glyoxalase system in astrocytes was associated with lower accumulation of AGEs compared with neurons (as assessed by Western blotting), a sixfold greater resistance to MG toxicity, and the capacity to protect neurons against MG in a coculture system. In addition, Glo-1 downregulation using RNA interference strategies resulted in a loss of viability in neurons, but not in astrocytes. Finally, stimulation of neuronal glycolysis via lentiviral-mediated overexpression of 6-phosphofructose-2-kinase/fructose-2,6-bisphosphatase-3 resulted in increased MG levels and MG-modified proteins. Since MG is largely produced through glycolysis, this suggests that the poor capacity of neurons to upregulate their glycolytic flux as compared with astrocytes may be related to weaker defense mechanisms against MG toxicity. Accordingly, the neuroenergetic specialization taking place between these two cell types may serve as a protective mechanism against MG-induced neurotoxicity.

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Neurotoxicity of methylglyoxal and 3-deoxyglucosone on cultured cortical neurons: Synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases

Cited by 129 publications

References 36 publications

Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Identification and Determination of α-Dicarbonyl Compounds Formed in the Degradation of Sugars

Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection

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