The Functions of Thioredoxin 1 in Neurodegeneration

Bai, Jie; Awan, Maher Un Nisa; Yan, Fang; Mahmood, Faisal; Bai, Liping; Liu, Jingyu

doi:10.1089/ars.2021.0186

Cited by 13 publications

(12 citation statements)

References 142 publications

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“…A bioinformatic analysis of the rat transcriptomic data using IPA® identified a network of genes, where their protein products are involved in inflammation and programmed cell death, including apoptosis (Cytochome c) [ 24 ] and pyroptosis (Caspase 1 and 4) [ 25 ] as well as the antioxidant factor Thioredoxin 1 [ 26 ], which also has an important role in the defence of neurons [ 27 ]. The genes Cycs , Casp4 , Casp1 , and Txn1 were all upregulated in the SNL rat within the range of fold change 1.27–1.34; p -value < 0.05.…”

Section: Resultsmentioning

confidence: 99%

The Identification of Human Translational Biomarkers of Neuropathic Pain and Cross-Species Validation Using an Animal Model

et al. 2022

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Neuropathic pain is a common chronic condition, which remains poorly understood. Many patients receiving treatment continue to experience severe pain, due to limited diagnostic/treatment management programmes. The development of objective clinical diagnostic/treatment strategies requires identification of robust biomarkers of neuropathic pain. To this end, we looked to identify biomarkers of chronic neuropathic pain by assessing gene expression profiles in an animal model of neuropathic pain, and differential gene expression in patients to determine the potential translatability. We demonstrated cross-species validation of several genes including those identified through bioinformatic analysis by assessing their expression in blood samples from neuropathic pain patients, according to conservative assessments of significance measured using Bonferroni-corrected p-values. These include CASP5 (p = 0.00226), CASP8 (p = 0.00587), CASP9 (p = 2.09 × 10−9), FPR2 (p = 0.00278), SH3BGRL3 (p = 0.00633), and TMEM88 (p = 0.00038). A ROC analysis revealed several combinations of genes to show high levels of discriminatory power in the comparison of neuropathic pain patients and control participants, of which the combination SH3BGRL3, TMEM88, and CASP9 achieved the highest level (AUROC = 0.923). The CASP9 gene was found to be common in five combinations of three genes revealing the highest levels of discriminatory power. In contrast, the gene combination PLAC8, ROMO1, and A3GALT2 showed the highest levels of discriminatory power in the comparison of neuropathic pain and nociceptive pain (AUROC = 0.919), when patients were grouped by S-LANSS scores. Molecules that demonstrate an active role in neuropathic pain have the potential to be developed into a biological measure for objective diagnostic tests, or as novel drug targets for improved pain management.

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Section: Resultsmentioning

confidence: 99%

The Identification of Human Translational Biomarkers of Neuropathic Pain and Cross-Species Validation Using an Animal Model

et al. 2022

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“… 31 In the central nervous system, Trx1 could be involved in developing of several neurodegenerative diseases, including Alzheimer's, Huntington's, and Parkinson's diseases. 32 To investigate whether Cirbp could target Trx1 to improve hippocampal damage in PND mice, we examined Trx1 levels in the hippocampus. The results showed that although the level of Trx1 mRNA was unchanged in each group, the Trx1 protein level was lower in the surgery group than in the sham group, whereas the upregulation of Cirbp expression increased Trx1 levels.…”

Section: Discussionmentioning

confidence: 99%

The cold‐inducible RNA‐binding protein—Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin‐related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction

Huang,

Zhu,

Liu

et al. 2023

CNS Neurosci Ther

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BackgroundAs a multi‐disease model, neuroinflammation, mitochondrial dysfunction, and oxidative stress might be involved in the pathogenic process of perioperative neurocognitive dysfunction (PND). Dynamin‐related protein 1 (Drp1) could mediate mitochondrial fission and play important roles in mitochondrial dynamic homeostasis and mitochondria function. The Drp1 may be involved in PND development. The cold‐inducible RNA‐binding protein (Cirbp) could bind to the 3’‐UTR of the thioredoxin 1 (Trx1) mRNA, control oxidative stress, and improve mitochondrial function. In this study, we hypothesized that the Cirbp‐Trx1 pathway could ameliorate mitochondrial dysfunction and Drp1 levels in PND mice.MethodsDifferentially expressed genes were screened using the Gene Expression Omnibus (GEO) database GSE95426 and validated using PCR. Eighteen‐month‐old C57BL/6 mice were subjected to tibial fracture surgery to generate a PND model. Cirbp was upregulated by hippocampal stereotaxic injections of over‐Cirbp plasmid according to the manufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression was measured using western blot (WB) and immunofluorescence (IF). The Morris water maze (MWM) was used to assess cognitive function. After behavioral testing, the hippocampal tissue was extracted to examine changes in mitochondrial Drp1, mitochondrial function, neuroinflammation, and oxidative stress.ResultsDifferential gene screening showed that Cirbp expression was significantly downregulated (fold change >1.5, p = 0.003272) in the PND model. In this study, we also found that Cirbp protein levels were downregulated, accompanied by an impairment of cognition, a decrease in superoxide dismutase (SOD) activity, and an increase in malondialdehyde (MDA) content, mitochondrial Drp1 levels, neuroinflammation, and apoptosis. Cirbp overexpression increased Trx1 protein levels and reversed the damage. However, this protective effect was abolished by PX‐12 treatment with a Trx1 inhibitor.ConclusionsThe Cirbp‐Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.

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“…In cardiovascular diseases, alterations in the thioredoxin system may affect the oxidative stress response, inflammatory response, and endothelial function of cardiomyocytes, thereby participating in the formation of diseases such as atherosclerosis and myocardial infarction [ 107 , 108 ]. In the case of neurodegenerative diseases, the thioredoxin system plays a key role in protecting neuronal cells from oxidative damage and maintaining neural system functions [ 109 , 110 ]. Given the critical role of the thioredoxin system in these diseases, we speculate that TRXR1-specific inhibitors, by affecting the thioredoxin system and thus disulfide bonds, may also be applicable to cancer, cardiovascular diseases and CNS diseases.…”

Section: The Regulatory Network Of Disulfidptosismentioning

confidence: 99%

Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions

Chen,

Ma,

Yang

et al. 2024

Biomark Res

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Cell death is an important part of the life cycle, serving as a foundation for both the orderly development and the maintenance of physiological equilibrium within organisms. This process is fundamental, as it eliminates senescent, impaired, or aberrant cells while also promoting tissue regeneration and immunological responses. A novel paradigm of programmed cell death, known as disulfidptosis, has recently emerged in the scientific circle. Disulfidptosis is defined as the accumulation of cystine by cancer cells with high expression of the solute carrier family 7 member 11 (SLC7A11) during glucose starvation. This accumulation causes extensive disulfide linkages between F-actins, resulting in their contraction and subsequent detachment from the cellular membrane, triggering cellular death. The RAC1-WRC axis is involved in this phenomenon. Disulfidptosis sparked growing interest due to its potential applications in a variety of pathologies, particularly oncology, neurodegenerative disorders, and metabolic anomalies. Nonetheless, the complexities of its regulatory pathways remain elusive, and its precise molecular targets have yet to be definitively identified. This manuscript aims to meticulously dissect the historical evolution, molecular underpinnings, regulatory frameworks, and potential implications of disulfidptosis in various disease contexts, illuminating its promise as a groundbreaking therapeutic pathway and target.

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The Functions of Thioredoxin 1 in Neurodegeneration

Cited by 13 publications

References 142 publications

The Identification of Human Translational Biomarkers of Neuropathic Pain and Cross-Species Validation Using an Animal Model

The Identification of Human Translational Biomarkers of Neuropathic Pain and Cross-Species Validation Using an Animal Model

The cold‐inducible RNA‐binding protein—Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin‐related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction

Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions

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