ArticleAutophagy2015
Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorder: an integrated study combining meta-analysis, network pharmacology, and computational biology.BMC pharmacology & toxicology · 2025Pooled it
- Zebrafish Models of Parkinson's Disease: From Pathogenesis to Drug Discovery.International journal of molecular sciences · 2026Review
- The role of energy deficit in autophagy failure in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Insights into the cellular function and mechanism of action of quinone reductase 2 (NQO2).The Biochemical journal · 2025Review
- Zinc finger protein 800 (ZNF800) promotes proliferation and migration of lower-grade glioma and is associated with immune infiltration.PloS one · 2025Article
- Bioenergetic-related gene expression in the hippocampus predicts internalizing vs. externalizing behavior in an animal model of temperament.Frontiers in molecular neuroscience · 2025Article
- Neuroprotective effects ofJournal of traditional and complementary medicine · 2024Article
- Polymorphisms and Pharmacogenomics ofGenes · 2024Review
- The specific NQO2 inhibitor, S29434, only marginally improves the survival of dopamine neurons in MPTP-intoxicated mice.Journal of neural transmission (Vienna, Austria : 1996) · 2024Article
- Unravelling the role of gut microbiota in acute pancreatitis: integrating Mendelian randomization with a nested case-control study.Frontiers in microbiology · 2024Article
- Autophagy and neuroprotection in astrocytes exposed to 6-hydroxydopamine is negatively regulated by NQO2: relevance to Parkinson's disease.Scientific reports · 2023Article
- The influence of NQO2 on the dysfunctional autophagy and oxidative stress induced in the hippocampus of rats and in SH-SY5Y cells by fluoride.CNS neuroscience & therapeutics · 2023Article
- Nutriepigenomics in Environmental-Associated Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Role of Astrocytes in Parkinson's Disease Associated with Genetic Mutations and Neurotoxicants.Cells · 2023Review
- Neuroglia Cells Transcriptomic in Brain Development, Aging and Neurodegenerative Diseases.Aging and disease · 2023Review
- Pesticides and the Microbiome-Gut-Brain Axis: Convergent Pathways in the Pathogenesis of Parkinson's Disease.Journal of Parkinson's disease · 2023Review
- Review
- Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson's disease.Neural regeneration research · 2022Article
- NGF Modulates Cholesterol Metabolism and Stimulates ApoE Secretion in Glial Cells Conferring Neuroprotection against Oxidative Stress.International journal of molecular sciences · 2022Article
- Paraquat Inhibits Autophagy Via Intensifying the Interaction Between HMGB1 and α-Synuclein.Neurotoxicity research · 2022Article
Corrections and comments
- Erratum issuedErratum.2017
Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular target of neurotoxins in the brain. PQ decreased the basal levels of LC3-II and LC3-positive vesicles, and its colocalization with lysosomal markers, both in the absence and presence of chloroquine. This was paralleled by increased number and size of SQSTM1/p62 aggregates. Downregulation of autophagy was also observed in cells chronically exposed to hydrogen peroxide or nonlethal concentrations of PQ, and it was associated with a reduced astrocyte capability to protect dopaminergic cells from OS in co-cultures. Surprisingly, PQ treatment led to inhibition of MTOR, activation of MAPK8/JNK1 and MAPK1/ERK2-MAPK3/ERK1 and upregulation of BECN1/Beclin 1 expression, all signals typically correlating with induction of autophagy. Reduction of OS by NMDPEF, a specific NQO2 inhibitor, but not by N-acetylcysteine, abrogated the inhibitory effect of PQ and restored autophagic flux. Activation of NQO2 by PQ or menadione and genetic manipulation of its expression confirmed the role of this enzyme in the inhibitory action of PQ on autophagy. PQ did not induce NFE2L2/NRF2, but when it was co-administered with NMDPEF NFE2L2 activity was enhanced in a SQSTM1-independent fashion. Thus, a prolonged OS in astrocytes inhibits LC3 lipidation and impairs autophagosome formation and autophagic flux, in spite of concomitant activation of several pro-autophagic signals. These findings outline an unanticipated neuroprotective role of astrocyte autophagy and identify in NQO2 a novel pharmacological target for its positive modulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.