Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic APPNL-G-F/NL-G-F mouse model

Upīte, Jolanta; Kadish, Inga; Groen, Thomas van; Jansone, Baiba

doi:10.1016/j.brainres.2020.147022

Cited by 5 publications

(2 citation statements)

References 52 publications

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“…Auranofin (AFN) is usually considered safe because of its favorable side effect profile and therapeutic effects [ 12 , 13 ]. Auranofin was also tested in multiple inflammatory preclinical disease models and showed great potential to treat a variety of inflammatory immune conditions such as hepatitis, colitis, and Alzheimer’s disease through its antioxidant and anti-inflammatory actions [ 12 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Auranofin Modulates Thioredoxin Reductase/Nrf2 Signaling in Peripheral Immune Cells and the CNS in a Mouse Model of Relapsing–Remitting EAE

Al-Kharashi,

Al-Harbi,

Ahmad

et al. 2023

Biomedicines

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Multiple sclerosis (MS) is one of the most prevalent chronic inflammatory autoimmune diseases. It causes the demyelination of neurons and the subsequent degeneration of the central nervous system (CNS). The infiltration of leukocytes of both myeloid and lymphoid origins from the systemic circulation into the CNS triggers autoimmune reactions through the release of multiple mediators. These mediators include oxidants, pro-inflammatory cytokines, and chemokines which ultimately cause the characteristic plaques observed in MS. Thioredoxin reductase (TrxR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling plays a crucial role in the regulation of inflammation by modulating the transcription of antioxidants and the suppression of inflammatory cytokines. The gold compound auranofin (AFN) is known to activate Nrf2 through the inhibition of TrxR; however, the effects of this compound have not been explored in a mouse model of relapsing–remitting MS (RRMS). Therefore, this study explored the influence of AFN on clinical features, TrxR/Nrf2 signaling [heme oxygenase 1 (HO-1), superoxide dismutase 1 (SOD-1)] and oxidative/inflammatory mediators [IL-6, IL-17A, inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine] in peripheral immune cells and the CNS of mice with the RR type of EAE. Our results showed an increase in TrxR activity and a decrease in Nrf2 signaling in SJL/J mice with RR-EAE. The treatment with AFN caused the amelioration of the clinical features of RR-EAE through the elevation of Nrf2 signaling and the subsequent upregulation of the levels of antioxidants as well as the downregulation of oxidative/pro-inflammatory mediators in peripheral immune cells and the CNS. These data suggest that AFN may be beneficial in the treatment of RRMS.

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Section: Introductionmentioning

confidence: 99%

Auranofin Modulates Thioredoxin Reductase/Nrf2 Signaling in Peripheral Immune Cells and the CNS in a Mouse Model of Relapsing–Remitting EAE

Al-Kharashi,

Al-Harbi,

Ahmad

et al. 2023

Biomedicines

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“…Several studies have characterized the development of pathology, functional connectivity, and behavioral phenotypes of these mice under multiple conditions (Jafari et al, 2018 ; Latif-Hernandez et al, 2019 , 2020 ; Mehla et al, 2019 ; Upite et al, 2020 ). Of the studies using this for Aβ seeding, both studies found seeding accelerated Aβ deposition, but neither tested behavior of the mice following the seeding (Purro et al, 2018 ; Ruiz-Riquelme et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

The effect of Aβ seeding is dependent on the presence of knock-in genes in the AppNL−G−F mice

Lacoursiere

Safar²,

Westaway³

et al. 2022

Front. Dement.

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Alzheimer's disease (AD) is characterized by the prion-like propagation of amyloid-β (Aβ). However, the role of Aβ in cognitive impairment is still unclear. To determine the causal role of Aβ in AD, we intracerebrally seeded the entorhinal cortex of a 2-month-old AppNL−G−F mouse model with an Aβ peptide derived from patients who died from rapidly progressing AD. When the mice were 3 months of age or 1 month following seeding, spatial learning and memory were tested using the Morris water task. Immunohistochemical labeling showed seeding with the Aβ was found accelerate Aβ plaque deposition and microgliosis in the AppNL−G−F mice, but this was dependent on the presence of the knocked-in genes. However, we found no correlation between pathology and spatial performance. The results of the present study show the seeding effects in the AppNL−G−F knock-in model, and how these are dependent on the presence of a humanized App gene. But these pathological changes were not initially causal in memory impairment.

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Auranofin-loaded PLGA nanoparticles alleviate cognitive deficit induced by streptozotocin in rats model: modulation of oxidative stress, neuroinflammatory markers, and neurotransmitters

Kushawaha,

Ashawat,

Baldi

2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic APPNL-G-F/NL-G-F mouse model

Cited by 5 publications

References 52 publications

Auranofin Modulates Thioredoxin Reductase/Nrf2 Signaling in Peripheral Immune Cells and the CNS in a Mouse Model of Relapsing–Remitting EAE

Auranofin Modulates Thioredoxin Reductase/Nrf2 Signaling in Peripheral Immune Cells and the CNS in a Mouse Model of Relapsing–Remitting EAE

The effect of Aβ seeding is dependent on the presence of knock-in genes in the AppNL−G−F mice

Auranofin-loaded PLGA nanoparticles alleviate cognitive deficit induced by streptozotocin in rats model: modulation of oxidative stress, neuroinflammatory markers, and neurotransmitters

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