ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
Akt Phosphorylates NQO1 and Triggers its Degradation, Abolishing Its Antioxidative Activities in Parkinson's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Tyrosine residues at the substrate binding site in human NQO1 homodimer: Protein conformational dynamics and optimization of substrate binding geometry.The FEBS journal · 2026Article
- Sex-dependent impact ofGenes & diseases · 2026Article
- Deletion of the SHORT Syndrome Gene Prkce Results in Brain Atrophy and Cognitive and Motor Behavior Deficits in Mice.Neuroscience bulletin · 2026Article
- Dual Neuroprotective and Nephroprotective Effects ofInternational journal of molecular sciences · 2026Article
- TBK1-NQO1 negative feedback loop regulates antiviral innate immunity.Cell communication and signaling : CCS · 2026Article
- Unravelling the novel insights between miR-7 and Parkinson's disease (PD).Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Sources of Oxidative Stress in Parkinson's Disease: Pathways and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Systematic Characterization of LUHMES Cell-Based Parkinson's Disease Models Reveals Potential Novel Drug Targets.Molecular neurobiology · 2025Article
- Improving Alzheimer's Disease and Parkinson's Disease in Rats with Nanoemulsion and Byproducts Prepared from Cinnamon Leaves.Pharmaceutics · 2025Article
- Parkinson Disease Signaling Pathways, Molecular Mechanisms, and Potential Therapeutic Strategies: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Environmental Factors Exacerbate Parkinsonian Phenotypes in an Asian-Specific Knock-In LRRK2 Risk Variant in Mice.International journal of molecular sciences · 2025Article
- Type 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors.Neuroscience bulletin · 2025Review
- Park7 deletion leads to sex-specific transcriptome changes involving NRF2-CYP1B1 axis in mouse midbrain astrocytes.NPJ Parkinson's disease · 2025Article
- VPS35 D620N mutation impairs neurogenesis and promotes ferroptosis in Parkinson's disease by using molecular docking, molecular dynamic simulation, and cellular model.Frontiers in aging neuroscience · 2025Article
- Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases.Journal of nanobiotechnology · 2024Review
- Impact of NQO1 dysregulation in CNS disorders.Journal of translational medicine · 2024Review
- Role of NADPH Quinone Reductase 1 (NQO1) Polymorphism in Prevention, Diagnosis, and Treatment of Gastrointestinal Cancers.Current cancer drug targets · 2024Review
- Paraquat and Parkinson's Disease: The Molecular Crosstalk of Upstream Signal Transduction Pathways Leading to Apoptosis.Current neuropharmacology · 2024Review
- Inhibition of abnormal C/EBPβ/α-Syn signaling pathway through activation of Nrf2 ameliorates Parkinson's disease-like pathology.Aging cell · 2023Article
- The Involvement of Neuroinflammation in the Onset and Progression of Parkinson's Disease.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The oxidative metabolism of dopamine and consequent oxidative stress are implicated in dopaminergic neuronal loss, mediating the pathogenesis of Parkinson's disease (PD). The inducible detoxifying antioxidative enzyme Quinone oxidoreductase (NQO1) (NAD(P)H: quinone oxidoreductase 1), neuroprotective to counteract reactive oxidative species, is most prominent in the active stage of the disease and virtually absent at the end stage of the disease. However, the molecular mechanism dictating NQO1 expression oscillation remains unclear. Here we show that Akt phosphorylates NQO1 at T128 residues and triggers its polyubiquitination and proteasomal degradation, abrogating its antioxidative effects in PD. Akt binds NQO1 in a phosphorylation-dependent manner. Interestingly, Akt, but not PINK1, provokes NQO1 phosphorylation and polyubiquitination with Parkin as an E3 ligase. Unphosphorylatable NQO1 mutant displays more robust neuroprotective activity than WT NQO1 in suppressing reactive oxidative species and against MPTP-induced dopaminergic cell death, rescuing the motor disorders in both α-synuclein transgenic transgenic male and female mice elicited by the neurotoxin. Thus, our findings demonstrate that blockade of Akt-mediated NQO1 degradation may ameliorate PD pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.