ArticleNeurobiology of aging2014
Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.
Article in Neurobiology of aging, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Breaking the age-related redox spiral for regeneration.Neural regeneration research · 2026Article
- Treatment of age-related decreases in GTP levels restores endocytosis and autophagy.GeroScience · 2026Article
- Investigating the oxidative stress-vascular brain injury axis in mild cognitive impairment of the Alzheimer's type.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- CNEURO-201, an Anti-amyloidogenic Agent and σ1-Receptor Agonist, Improves Cognition in theInternational journal of molecular sciences · 2025Article
- Age-Related Oxidative Redox and Metabolic Changes Precede Intraneuronal Amyloid-β Accumulation and Plaque Deposition in a Transgenic Alzheimer's Disease Mouse Model.Journal of Alzheimer's disease : JAD · 2022Article
- The impact of chronic exposure to air pollution over oxidative stress parameters and brain histology.Environmental science and pollution research international · 2021Article
- Brain Energy Deficit as a Source of Oxidative Stress in Migraine: A Molecular Basis for Migraine Susceptibility.Neurochemical research · 2021Review
- The role of Bcl-2 proteins in modulating neuronal CaBiochimica et biophysica acta. Molecular cell research · 2021Review
- RTA-408 protects against propofol-induced cognitive impairment in neonatal mice via the activation of Nrf2 and the inhibition of NF-κB p65 nuclear translocation.Brain and behavior · 2021Article
- Exploration of multi-target effects of 3-benzoyl-5-hydroxychromen-2-one in Alzheimer's disease cell and mouse models.Aging cell · 2020Article
- Age-Related Intraneuronal Aggregation of Amyloid-β in Endosomes, Mitochondria, Autophagosomes, and Lysosomes.Journal of Alzheimer's disease : JAD · 2020Article
- Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer's disease from a ferroptosis perspective.Progress in neurobiology · 2020Review
- Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease.Journal of bioenergetics and biomembranes · 2019Review
- Mini-GAGR, an intranasally applied polysaccharide, activates the neuronal Nrf2-mediated antioxidant defense system.The Journal of biological chemistry · 2018Article
- A Role for Nrf2 Expression in Defining the Aging of Hippocampal Neural Stem Cells.Cell transplantation · 2018Article
- Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?Antioxidants (Basel, Switzerland) · 2017Review
- Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer's Disease?International journal of molecular sciences · 2017Review
- Vitamin D, reactive oxygen species and calcium signalling in ageing and disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Review
- Chemical and Physical Approaches to Extend the Replicative and Differentiation Potential of Stem Cells.Stem cell reviews and reports · 2016Review
- Glutathione-induced drought stress tolerance in mung bean: coordinated roles of the antioxidant defence and methylglyoxal detoxification systems.AoB PLANTS · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible.
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