ArticleEndocrinology2019
NADPH Oxidase Mediates Membrane Androgen Receptor-Induced Neurodegeneration.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- Dihydrotestosterone-androgen receptor signaling suppresses EBV-positive gastric cancer through DNA demethylation-mediated viral reactivation.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Oxidative stress as a catalyst in prostate cancer progression: unraveling molecular mechanisms and exploring therapeutic interventions.Discover oncology · 2025Review
- The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats.Biology of sex differences · 2025Article
- The impact of chronic intermittent hypoxia on enzymatic activity in memory-associated brain regions of male and female rats.Research square · 2024Article
- Mitochondrion-based organellar therapies for central nervous system diseases.Cell communication and signaling : CCS · 2024Review
- NADPH oxidase 4-derived hydrogen peroxide counterbalances testosterone-induced endothelial dysfunction and migration.American journal of physiology. Endocrinology and metabolism · 2024Article
- Novel Plasma Membrane Androgen Receptor SLC39A9 Mediates Ovulatory Changes in Cells of the Monkey Ovarian Follicle.Endocrinology · 2024Article
- Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases.Journal of nanobiotechnology · 2024Review
- Chronic intermittent hypoxia-induced hypertension: the impact of sex hormones.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Review
- Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.Advanced pharmaceutical bulletin · 2024Review
- Impact of sex and hypoxia on brain region-specific expression of membrane androgen receptor AR45 in rats.Frontiers in endocrinology · 2024Article
- Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia.Biology of sex differences · 2023Article
- Article
- The Role of Lipid Rafts and Membrane Androgen Receptors in Androgen's Neurotoxic Effects.Journal of the Endocrine Society · 2022Article
- Cyanidin 3-O-arabinoside suppresses DHT-induced dermal papilla cell senescence by modulating p38-dependent ER-mitochondria contacts.Journal of biomedical science · 2022Article
- Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress.Endocrinology · 2021Review
- Ginsenoside Rg1 alleviates lipopolysaccharide-induced neuronal damage by inhibiting NLRP1 inflammasomes in HT22 cells.Experimental and therapeutic medicine · 2021Article
- Sexual fate of murine external genitalia development: Conserved transcriptional competency for male-biased genes in both sexes.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Neuroprotective and neurotoxic outcomes of androgens and estrogens in an oxidative stress environment.Biology of sex differences · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative stress (OS) is a common characteristic of several neurodegenerative disorders, including Parkinson disease (PD). PD is more prevalent in men than in women, indicating the possible involvement of androgens. Androgens can have either neuroprotective or neurodamaging effects, depending on the presence of OS. Specifically, in an OS environment, androgens via a membrane-associated androgen receptor (mAR) exacerbate OS-induced damage. To investigate the role of androgens on OS signaling and neurodegeneration, the effects of testosterone and androgen receptor activation on the major OS signaling cascades, the reduced form of NAD phosphate (NADPH) oxidase (NOX)1 and NOX2 and the Gαq/inositol trisphosphate receptor (InsP3R), were examined. To create an OS environment, an immortalized neuronal cell line was exposed to H2O2 prior to cell-permeable/cell-impermeable androgens. Different inhibitors were used to examine the role of G proteins, mAR, InsP3R, and NOX1/2 on OS generation and cell viability. Both testosterone and DHT/3-O-carboxymethyloxime (DHT)-BSA increased H2O2-induced OS and cell death, indicating the involvement of an mAR. Furthermore, classical AR antagonists did not block testosterone's negative effects in an OS environment. Because there are no known antagonists specific for mARs, an AR protein degrader, ASC-J9, was used to block mAR action. ASC-J9 blocked testosterone's negative effects. To determine OS-related signaling mediated by mAR, this study examined NOX1, NOX2, Gαq. NOX1, NOX2, and the Gαq complex with mAR. Only NOX inhibition blocked testosterone-induced cell loss and OS. No effects of blocking either Gαq or G protein activation were observed on testosterone's negative effects. These results indicate that androgen-induced OS is via the mAR-NOX complex and not the mAR-Gαq complex.
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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.