Involvement of glutaredoxin-1 and thioredoxin-1 in β-amyloid toxicity and Alzheimer's disease

Akterin, Susanne; Cowburn, Richard F.; Miranda‐Vizuete, Antonio; Jiménez, Alberto; Bogdanović, Nenad; Winblad, Bengt; Cedazo-Minguez, Ángel

doi:10.1038/sj.cdd.4401818

Cited by 164 publications

(142 citation statements)

References 39 publications

(63 reference statements)

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“…Grx1 resides mainly in the cytosol, although it may translocate into the nucleus in response to certain stimuli. For example, in the brains of patients with Alzheimer disease, control samples revealed Grx1 was located mainly in the cytosolic compartment, contrary to the nuclear staining in Alzheimer disease neurons (16). In our study nuclear translocation of Grx1 was evident in FAP salivary glands (indicated by arrows in Figure 2).…”

Section: Tissue Markers For Oxidative Stressmentioning

confidence: 59%

“…Despite the importance of Grx1 and Trx1 as regulators of oxidative stress and apoptosis, their role in FAP is completely unknown. We believe that overexpression of Grx1 may have a protective role, acting to detoxify FAP tissues as it does the frontal cortex and hippocampal neurons of the brain in Alzheimer disease (16). Trx1 was not up-regulated in the analyzed tissues with TTR deposition, except for DRG, probably because salivary glands and stomach mucosa are in contact with multiple stimuli and irritations.…”

Section: Discussionmentioning

confidence: 90%

“…The biomarker 8-OHdG, a modified base that occurs in DNA due to attack by hydroxyl radicals formed as byproducts and intermediates of aerobic metabolism and during oxidative stress, has been increasingly used as a sensitive, stable, and integral marker of oxidative damage in cellular DNA (19). In a neuroblastoma cell line, Aβ fibrils caused transient oxidation of both Grx1 and Trx1 (16). Cytosolic mammalian Trx1 has numerous functions in defense against oxidative stress, control of growth, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Biomarkers in the Assessment of Therapies for Familial Amyloidotic Polyneuropathy

Macedo

Batista

Amaral

et al. 2007

Mol Med

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The identification of specific biomarkers provides opportunities to develop early diagnostic parameters, monitor disease progression, and test drug efficiency in clinical trials. We previously demonstrated that in familial amyloidotic polyneuropathy (FAP) related to the abnormal extracellular tissue deposition of mutant transthyretin (TTR), inflammatory and apoptotic pathways are triggered in the presymptomatic stages of the disease, when nonfibrillar TTR deposits are present. In the present work, to better define biomarkers for future assessment of prophylactic and therapeutic drugs in the treatment of FAP, we extended the search for oxidative stress and apoptotic biomarkers to clinical samples and animal models presenting nonfibrillar and fibrillar TTR. We found that lipid peroxidation measured by hydroxynonenal, oxidative DNA damage measured by 8-hydroxy-2′-deoxyguanosine, and cellular redox homeostasis measured by glutaredoxin 1 were consistently increased in biopsy specimens from FAP patients and in tissues from transgenic mouse models presenting nonfibrillar TTR deposition. Death-receptor Fas, caspase-8, and Bax were also found to be increased, indicative of the involvement of death receptors in the observed apoptosis process. Removal of TTR deposition by an immunization protocol resulted in significant decreases of the selected markers we describe, corroborating the relationship between TTR deposition, oxidative stress, and apoptosis. Taken together, our results provide a robust biomarker profile for initial experimental animal studies and clinical trials to assess the application of the selected markers in therapies aimed at removal and/or inhibition of TTR polymerization.

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Section: Tissue Markers For Oxidative Stressmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Biomarkers in the Assessment of Therapies for Familial Amyloidotic Polyneuropathy

Macedo

Batista

Amaral

et al. 2007

Mol Med

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“…142 Accordingly, GRX1 overexpression protects against amyloid b-induced toxicity. 143 PD progression is associated with a depletion of GSH levels and an increase in ROS formation in the substantia nigra. In fact GSH depletion has been proposed as one of the early biochemical events associated with neuronal apoptosis in PD.…”

Section: Gsh Apoptosis and Disease Progressionmentioning

confidence: 99%

Apoptosis and glutathione: beyond an antioxidant

2009

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Apoptosis is a conserved homeostatic process critical for organ and tissue morphogenesis, development, and senescence. This form of programmed cell death also participates in the etiology of several human diseases including cancer, neurodegenerative, and autoimmune disorders. Although the signaling pathways leading to the progression of apoptosis have been extensively characterized, recent studies highlight the regulatory role of changes in the intracellular milieu (permissive apoptotic environment) in the efficient activation of the cell death machinery. In particular, glutathione (GSH) depletion is a common feature of apoptotic cell death triggered by a wide variety of stimuli including activation of death receptors, stress, environmental agents, and cytotoxic drugs. Although initial studies suggested that GSH depletion was only a byproduct of oxidative stress generated during cell death, recent discoveries suggest that GSH depletion and post-translational modifications of proteins through glutathionylation are critical regulators of apoptosis. Here, we reformulate these emerging paradigms into our current understanding of cell death mechanisms. Apoptosis or programmed cell death is a ubiquitous homeostatic process involved in numerous biological systems. Under physiological conditions it is critical not only in the turnover of cells in tissues but also during normal development and senescence. Moreover, its deregulation has been widely observed to occur as either a cause or consequence of distinct pathologies including cancer, autoimmune, and neurodegenerative diseases. Apoptosis is a highly organized program induced by a myriad of stimuli that are characterized by the progressive activation of precise pathways leading to specific biochemical and morphological alterations in individual cells without involving an inflammatory response. Early stages of apoptosis are characterized by initiator caspase activation, cell shrinkage, loss of plasma membrane lipid asymmetry, and chromatin condensation. The execution phase of apoptosis is characterized by activation of executioner caspases and endonucleases, apoptotic body formation, and cell fragmentation 1 (Figure 1). Interestingly, recent studies have shown that changes in the intracellular milieu of the cells, such as alterations in the redox environment, are important regulators of the progression to apoptosis. 2 These discoveries have lead to the concept of a permissive apoptotic environment necessary for the activation of the proper signaling pathways regulating apoptosis. Glutathione (GSH) depletion is an early hallmark in the progression of cell death in response to a variety of apoptotic stimuli in numerous cell types 3,4 (Figure 2), although the exact role of GSH depletion in apoptosis is still controversial. We review recent data that show new insights into the understanding of the causes and consequences that alterations in the redox environment of the cell have on apoptosis.The Role of GSH in the Regulation of Apoptosis GSH synthesis, depletion, and apopt...

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“…The antioxidant defenses include vitamins, minerals, and the antioxidant enzymes glutathione, superoxide dismutase, hydrogen peroxidase, catalase, and thioredoxins (8). The protection of thioredoxin 1 (TRX1) 1 against retinal photooxidative damage (9) and its role in neurodegenerative diseases like Alzheimer disease are known (10,11). TRX1, the substrate of thioredoxin reductase, can protect neuronal cells by scavenging free radicals, binding and inhibiting apoptosis signal-regulating kinase 1 (12), regulating transcription factors, and maintaining redox homeostasis (13).…”

mentioning

confidence: 99%

The Thioredoxin-like Protein Rod-derived Cone Viability Factor (RdCVFL) Interacts with TAU and Inhibits Its Phosphorylation in the Retina

Fridlich

Delalande

Jaillard

et al. 2009

Molecular & Cellular Proteomics

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Rod-derived cone viability factor (RdCVF) is produced by the Nxnl1 gene that codes for a second polypeptide, RdCVFL, by alternative splicing. Although the role of RdCVF in promoting cone survival has been described, the implication of RdCVFL, a putative thioredoxin enzyme, in the protection of photoreceptors is presently unknown. Using a proteomics approach we identified 90 proteins interacting with RdCVFL including the microtubule-binding protein TAU. We demonstrate that the level of phosphorylation of TAU is increased in the retina of the Nxnl1 ؊/؊ mice as it is hyperphosphorylated in the brain of patients suffering from Alzheimer disease, presumably in some cases through oxidative stress. Using a cell-based assay, we show that RdCVFL inhibits TAU phosphorylation. In vitro, RdCVFL protects TAU from oxidative damage. Photooxidative stress is implicated in retinal degeneration, particularly in retinitis pigmentosa, where it is considered to be a contributor to secondary cone death. The functional interaction between RdCVFL and TAU described here is the first characterization of the RdCVFL signaling pathway involved in neuronal cell death mediated by oxidative stress.

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Involvement of glutaredoxin-1 and thioredoxin-1 in β-amyloid toxicity and Alzheimer's disease

Cited by 164 publications

References 39 publications

Biomarkers in the Assessment of Therapies for Familial Amyloidotic Polyneuropathy

Biomarkers in the Assessment of Therapies for Familial Amyloidotic Polyneuropathy

Apoptosis and glutathione: beyond an antioxidant

The Thioredoxin-like Protein Rod-derived Cone Viability Factor (RdCVFL) Interacts with TAU and Inhibits Its Phosphorylation in the Retina

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