Age- and stage-dependent glyoxalase I expression and its activity in normal and Alzheimer's disease brains

Kuhla, Björn; Boeck, Katharina; Schmidt, Angela; Ogunlade, Vera; Arendt, Thomas; Münch, Gerald; Lüth, Hans-Joachim

doi:10.1016/j.neurobiolaging.2005.11.007

Cited by 101 publications

(77 citation statements)

References 36 publications

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“…Impaired Glo-1 activity may thus contribute to the pathogenesis of neurodegenerative disorders, considering that MG induces oxidative stress and AGE formation, which are major factors involved in many of these agedependent pathologies. For example, in Alzheimer's disease (AD), Glo-1 expression is increased in early stages, but then decreases below normal levels at later stages, correlating with a marked increase in AGE accumulation Kuhla et al, 2007). AGEs colocalize with amyloid-␤ plaques and neurons containing hyperphosphorylated tau protein in AD brains, but astrocytes are also affected as they show increased AGE and inducible nitric oxide synthase immunoreactivity (Wong et al, 2001;Lüth et al, 2005).…”

mentioning

confidence: 99%

Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection

Bélanger

Yang²,

Petit³

et al. 2011

J. Neurosci.

104

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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mentioning

confidence: 99%

Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection

Bélanger

Yang²,

Petit³

et al. 2011

J. Neurosci.

104

131

View full text Add to dashboard Cite

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“…However, in the late stage of AD, the glyoxalase I level is decreased. Furthermore, in both age-and AD-affected brains the level of glyoxalase1 correlated with AGE deposits [49].…”

Section: Enzymes Involved In Defense Against Agesmentioning

confidence: 93%

“…Furthermore, it has been shown that glyoxylase I is involved in the catabolic pathway of methylglyoxal [48]. This enzyme levels decrease in the late stage of AD [49]. This leads to a build-up of high carbonyl stress, which increases the levels of AGEs, oxidative stress, inflammation, plaque and tangle formation, and finally apoptosis.…”

Section: Glycation In Alzheimer's Diseasementioning

confidence: 99%

The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach

Salahuddin

Rabbani

Khan

2014

Cellular and Molecular Biology Letters

148

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of advanced glycation end products; ROS -reactive oxygen species; SNCA -synuclein alpha; sRAGE -soluble receptor of advanced glycation end products; TTR -transthyretin; TKtransketolase; TNF -tumor necrosis factor-α; TPP -thiamine pyrophosphate Review THE ROLE OF ADVANCED GLYCATION END PRODUCTS IN VARIOUS TYPES OF NEURODEGENERATIVE DISEASE:A THERAPEUTIC APPROACH Abstract: Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies Unauthenticated Download Date | 5/11/18 1:17 PM

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“…In addition, RAGE has been shown to mediate mitochondrial dysfunction in neurons by transporting Aβ into the cells, which subsequently results in greater neuronal dysfunction and degeneration [64]. Atop the multiple mechanisms of augmented RAGE ligand production in AD, there is also prominent downregulation of specific detoxification mechanisms, which inhibit production of pre-AGEs such as methylglyoxal (MG) [65]. Glyoxalase 1 (GLO1), the principal enzyme that detoxifies MG, mitigates AGE production and is upregulated in the early and mid-stages of AD in human subjects.…”

Section: Consequences Of Rage Signal Transductionmentioning

confidence: 99%

“…Glyoxalase 1 (GLO1), the principal enzyme that detoxifies MG, mitigates AGE production and is upregulated in the early and mid-stages of AD in human subjects. However, in the late and progressive stages of AD dysfunction, depletion of the enzyme's chief and essential cofactor, glutathione, reduces overall activity of the GLO1-AGE detoxifying system, thus facilitating increased AGE production and accumulation [65,66]. Altogether, these findings underscore a potentially profound link between peripheral and central inflammation, which prompts the question: to what extent might anti-AGE/RAGE therapies provide protective measures for neurodegeneration and AD, given the prominence of cellular stress driven by increased RAGE ligand burden [67][68][69].…”

Section: Consequences Of Rage Signal Transductionmentioning

confidence: 99%