ArticleGlia2014
Subpicomolar diphenyleneiodonium inhibits microglial NADPH oxidase with high specificity and shows great potential as a therapeutic agent for neurodegenerative diseases.
Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- NADPH oxidases in Parkinson's disease: a systematic review.Molecular neurodegeneration · 2017Pooled it
- NOX-NOS crosstalk in the liver-brain axis: Novel insights for redox regulation and neurodegenerative diseases.Redox biology · 2025Review
- Identification and verification of key molecules in the epileptogenic process of focal cortical dysplasia.Metabolic brain disease · 2024Article
- What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson's Disease?International journal of molecular sciences · 2024Review
- Complement C3 Enhances LPS-Elicited Neuroinflammation and Neurodegeneration Via the Mac1/NOX2 Pathway.Molecular neurobiology · 2023Article
- The NADPH Oxidase Inhibitors Apocynin and Diphenyleneiodonium Protect Rats from LPS-Induced Pulmonary Inflammation.Antioxidants (Basel, Switzerland) · 2023Article
- High-throughput screening of caterpillars as a platform to study host-microbe interactions and enteric immunity.Nature communications · 2022Article
- Identification of significant modules and hub genes involved in hepatic encephalopathy using WGCNA.European journal of medical research · 2022Article
- IFNγ regulates NAD+ metabolism to promote the respiratory burst in human monocytes.Blood advances · 2022Article
- Activation of the MAC1-ERK1/2-NOX2 Pathway Is Required for LPS-Induced Sustaining Reactive Microgliosis, Chronic Neuroinflammation and Neurodegeneration.Antioxidants (Basel, Switzerland) · 2022Article
- NOX2-derived hydrogen peroxide impedes the AMPK/Akt-mTOR signaling pathway contributing to cell death in neuronal cells.Cellular signalling · 2022Article
- LncRNA, an Emerging Approach for Neurological Diseases Treatment by Regulating Microglia Polarization.Frontiers in neuroscience · 2022Review
- Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson's Disease.Frontiers in immunology · 2021Review
- Article
- Ultralow doses of dextromethorphan protect mice from endotoxin-induced sepsis-like hepatotoxicity.Chemico-biological interactions · 2019Article
- Inhibition of NADPH oxidase by apocynin prevents learning and memory deficits in a mouse Parkinson's disease model.Redox biology · 2019Article
- NADPH Oxidase Mediates Membrane Androgen Receptor-Induced Neurodegeneration.Endocrinology · 2019Article
- Iron accentuated reactive oxygen species release by NADPH oxidase in activated microglia contributes to oxidative stress in vitro.Journal of neuroinflammation · 2019Article
- Pharmacological Targeting of Microglial Activation: New Therapeutic Approach.Frontiers in cellular neuroscience · 2019Review
- The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Activation of microglial NADPH oxidase (NOX2) plays a critical role in mediating neuroinflammation, which is closely linked with the pathogenesis of a variety of neurodegenerative diseases, including Parkinson's disease (PD). The inhibition of NOX2-generated superoxide has become an effective strategy for developing disease-modifying therapies for PD. However, the lack of specific and potent NOX2 inhibitors has hampered the progress of this approach. Diphenyleneiodonium (DPI) is a widely used, long-acting NOX2 inhibitor. However, due to its non-specificity for NOX2 and high cytotoxicity at standard doses (µM), DPI has been precluded from human studies. In this study, using ultra-low doses of DPI, we aimed to: (1) investigate whether these problems could be circumvented and (2) determine whether ultra-low doses of DPI were able to preserve its utility as a potent NOX2 inhibitor. We found that DPI at subpicomolar concentrations (10(-14) and 10(-13) M) displays no toxicity in primary midbrain neuron-glia cultures. More importantly, we observed that subpicomolar DPI inhibited phorbol myristate acetate (PMA)-induced activation of NOX2. The same concentrations of DPI did not inhibit the activities of a series of flavoprotein-containing enzymes. Furthermore, potent neuroprotective efficacy was demonstrated in a post-treatment study. When subpicomolar DPI was added to neuron-glia cultures pretreated with lipopolysaccharide, 1-methyl-4-phenylpyridinium or rotenone, it potently protected the dopaminergic neurons. In summary, DPI's unique combination of high specificity toward NOX2, low cytotoxicity and potent neuroprotective efficacy in post-treatment regimens suggests that subpicomolar DPI may be an ideal candidate for further animal studies and potential clinical trials.
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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.