The Role of the Thioredoxin System in Brain Diseases

Bjørklund, Geir; Zou, Lili; Peana, Massimiliano; Chasapis, Christos T.; Tony, Hangan; Lu, Jun; Maes, Michaël

doi:10.3390/antiox11112161

Cited by 19 publications

(5 citation statements)

References 260 publications

(307 reference statements)

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“…In case of Lactobacillus casei , metabolites can enter the blood through the gastrointestinal epithelium and regulate antioxidant status in mice [28] . Notably, L. macroides G117 encodes the thioredoxin system, which consists of thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH, and plays a regulatory role in antioxidation, cell proliferation and apoptosis [29] . Additionally, L. macroides G117 produces heme oxygenase, a rate-limiting enzyme in heme degradation.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and anti-stress properties of postbiotics produced by Lysinibacillus macroides G117

Qiao,

Lv,

Zhang

et al. 2024

Comparative Immunology Reports

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Section: Discussionmentioning

confidence: 99%

Antioxidant and anti-stress properties of postbiotics produced by Lysinibacillus macroides G117

Qiao,

Lv,

Zhang

et al. 2024

Comparative Immunology Reports

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“…The above three enzymes are the most extensively studied enzymes for antioxidant stress in AD. However, studies of thioredoxin reductase and peroxiredoxin have long overshadowed antioxidant defenses in AD 49,50 . Peroxiredoxin can scavenge ROS, 49 thioredoxin reductase can neutralize hydrogen peroxide 50 .…”

Section: Discussionmentioning

confidence: 99%

“…However, studies of thioredoxin reductase and peroxiredoxin have long overshadowed antioxidant defenses in AD 49,50 . Peroxiredoxin can scavenge ROS, 49 thioredoxin reductase can neutralize hydrogen peroxide 50 . The Trx‐Prx system can be used as a promising biomarker for diagnosing AD 50 .…”

Section: Discussionmentioning

confidence: 99%

“… 49 , 50 Peroxiredoxin can scavenge ROS, 49 thioredoxin reductase can neutralize hydrogen peroxide. 50 The Trx‐Prx system can be used as a promising biomarker for diagnosing AD. 50 We also found that Icaritin restores the expression of 10 genes encoding the components of GST damaged by Aβ arc toxicity.…”

Section: Discussionmentioning

confidence: 99%

“… 50 The Trx‐Prx system can be used as a promising biomarker for diagnosing AD. 50 We also found that Icaritin restores the expression of 10 genes encoding the components of GST damaged by Aβ arc toxicity. GST has always been considered another important enzyme system for antioxidant stress.…”

Section: Discussionmentioning

confidence: 99%

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Icaritin greatly attenuates β‐amyloid‐induced toxicity in vivo

Li,

Wei,

Tang

et al. 2023

CNS Neurosci Ther

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AimsThe accumulation and deposition of β‐amyloid (Aβ) has always been considered a major pathological feature of Alzheimer's disease (AD). The latest and mainstream amyloid cascade hypothesis indicates that all the main pathological changes in AD are attributed to the accumulation of soluble Aβ. However, the exploration of therapeutic drugs for Aβ toxicity has progressed slowly. This study aims to investigate the protective effects of Icaritin on the Aβ‐induced Drosophila AD model and its possible mechanism.MethodsTo identify the effects of Icaritin on AD, we constructed an excellent Drosophila AD model named Aβarc (arctic mutant Aβ42) Drosophila. Climbing ability, flight ability, and longevity were used to evaluate the effects of Icaritin on AD phenotypes. Aβarc was determined by immunostaining and ELISA. To identify the effects of Icaritin on oxidative stress, we performed the detection of ROS, hydrogen peroxide, MDA, SOD, catalase, GST, and Caspase‐3. To identify the effects of Icaritin on energy metabolism, we performed the detection of ATP and lactate. Transcriptome analysis and qRT‐PCR verifications were used to detect the genes directly involved in oxidative stress and energy metabolism. Mitochondrial structure and function were detected by an electron microscopy assay, a mitochondrial membrane potential assay, and a mitochondrial respiration assay.ResultsWe discovered that Icaritin almost completely rescues the climbing ability, flight ability, and longevity of Aβarc Drosophila. Aβarc was dramatically reduced by Icaritin treatment. We also found that Icaritin significantly reduces oxidative stress and greatly improves impaired energy metabolism. Importantly, transcriptome analysis and qRT‐PCR verifications showed that many key genes, directly involved in oxidative stress and energy metabolism, are restored by Icaritin. Next, we found that Icaritin perfectly restores the integrity of mitochondrial structure and function damaged by Aβarc toxicity.ConclusionThis study suggested that Icaritin is a potential drug to deal with the toxicity of Aβarc, at least partially realized by restoring the mitochondria/oxidative stress/energy metabolism axis, and holds potential for translation to human AD.

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Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets

Ghatak,

Diedrich,

Talantova

et al. 2024

Advanced Science

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Standard single‐cell (sc) proteomics of disease states inferred from multicellular organs or organoids cannot currently be related to single‐cell physiology. Here, a scPatch‐Clamp/Proteomics platform is developed on single neurons generated from hiPSCs bearing an Alzheimer's disease (AD) genetic mutation and compares them to isogenic wild‐type controls. This approach provides both current and voltage electrophysiological data plus detailed proteomics information on single‐cells. With this new method, the authors are able to observe hyperelectrical activity in the AD hiPSC‐neurons, similar to that observed in the human AD brain, and correlate it to ≈1400 proteins detected at the single neuron level. Using linear regression and mediation analyses to explore the relationship between the abundance of individual proteins and the neuron's mutational and electrophysiological status, this approach yields new information on therapeutic targets in excitatory neurons not attainable by traditional methods. This combined patch‐proteomics technique creates a new proteogenetic‐therapeutic strategy to correlate genotypic alterations to physiology with protein expression in single‐cells.

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The Role of the Thioredoxin System in Brain Diseases

Cited by 19 publications

References 260 publications

Antioxidant and anti-stress properties of postbiotics produced by Lysinibacillus macroides G117

Antioxidant and anti-stress properties of postbiotics produced by Lysinibacillus macroides G117

Icaritin greatly attenuates β‐amyloid‐induced toxicity in vivo

Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets

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