Our study demonstrated that ferroptosis contributed to the toxicity of motor neurons and that activating NRF2 could alleviate neuronal degeneration in ALS with the hSOD1 G93A mutation.

Nov 1, 2019 · We demonstrated that inhibition of the thioredoxin-dependent system or copper-zinc superoxide dismutase (SOD1) could abrogate NRF2-mediated resistance to β-lapachone, while depletion of catalase or glutathione was ineffective.

Mice transiently depleted of SOD2 or overexpressing skeletal muscle-specific UCP1 exhibit Nrf2-mediated antioxidant gene expression and PGC1α-mediated mitochondrial biogenesis. ATF4 activation may induce a transcriptional program that enhances NADPH synthesis in the mitochondria and might cooperate with the Nrf2 antioxidant system.

A recent study by Miller et al. shows that specific knockdown of mutant SOD1 in the muscle alone has no effect on ALS pathology, whereas knockdown in the muscle and MNs together is sufficient to delay disease, suggesting that mutant SOD in the muscle is not a causative factor in ALS onset and progression [(Miller et al. 2006)]. Taking these ...

Nuclear factor erythroid 2-related factor 2 (Nrf2) is the transcriptional master regulator of cellular responses against oxidative stress.

Sep 1, 2021 · Genetic activation of NRF2 in astrocytes results in beneficial neuroprotective effects. The toxicity of astrocytes expressing ALS-linked mutant SOD1 to co-cultured MNs was reversed by NRF2 over-expression. NRF2 overexpression in astrocytes significantly delayed onset and extended survival in two ALS-mouse models [72, 232].

Oct 8, 2022 · Histochemical staining and transmission electron microscopy displayed pulmonary inflammation, collagen deposition, mitochondrial swelling, and a decreasing number of multilamellar bodies in alveolar type II cells after PM 2.5 exposure, which was related to PM 2.5 -induced oxidative stress.

Oct 28, 2019 · In human-derived astrocytes harboring mutant SOD1 causative of familial amyotrophic lateral sclerosis, we show that impaired ER redox signaling decreases Nrf2 nuclear translocation, resulting in ER calcium overload and increased calcium-dependent cell secretion, leading to motor neuron death.

Aug 1, 2023 · Our study demonstrated that ferroptosis contributed to the toxicity of motor neurons and that activating NRF2 could alleviate neuronal degeneration in ALS with the hSOD1G93A mutation. 1. Introduction. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder caused by increasing motor neuronal death.

Apr 7, 2009 · Immunoblots showed significant upregulation of superoxide dismutase 1 (SOD1), haem oxygenase 1, and catalase upon proteasome inhibition. Luciferase assays using a reporter driven by the SOD1 promoter revealed proteasome inhibitor-mediated induction of …