ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Regulation of the VHL/HIF-1 pathway by DJ-1.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production.BioMed research international · 2019Trial
- Progress of Immunotherapies in Parkinson's Disease.CNS neuroscience & therapeutics · 2026Review
- Neurobiology of exercise in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Hypoxia-inducible factor-1α: Dual roles in maintaining neuronal homeostasis and neuronal degeneration via regulation of oxidative stress, mitochondrial dynamics, and bioenergetics.Journal of physiology and biochemistry · 2026Review
- Molecular Mechanisms and Therapeutic Potential of DJ-1 in Skeletal Muscle Homeostasis and Disease.Comprehensive Physiology · 2026Review
- Alpinetin Targets Mitophagy Pathways to Mitigate Parkinson's Disease Progression.CNS neuroscience & therapeutics · 2025Article
- Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer.Cellular & molecular biology letters · 2025Review
- Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.International journal of molecular sciences · 2024Review
- Randomized controlled trial of intermittent hypoxia in Parkinson's disease: study rationale and protocol.BMC neurology · 2024Article
- The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.International journal of molecular sciences · 2024Review
- Identifying TRIM11 Upregulators as Therapeutic Targets in Alzheimer's Disease: A Bayesian Network Approach.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2024Article
- The neuroprotective effects of FG-4592, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, against oxidative stress induced by alpha-synuclein in N2a cells.Scientific reports · 2023Article
- Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us.International journal of molecular sciences · 2023Review
- Inhibition of carnitine palmitoyl-transferase 1 is a potential target in a mouse model of Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Atypical Ubiquitination and Parkinson's Disease.International journal of molecular sciences · 2022Review
- Dysregulation of Oxygen Sensing/Response Pathways in Pregnancies Complicated by Idiopathic Intrauterine Growth Restriction and Early-Onset Preeclampsia.International journal of molecular sciences · 2022Article
- Review
- Brief inhalation of sevoflurane can reduce glial scar formation after hypoxic-ischemic brain injury in neonatal rats.Neural regeneration research · 2021Article
- The Role of DJ-1 in Cellular Metabolism and Pathophysiological Implications for Parkinson's Disease.Cells · 2021Review
- PARK7 maintains the stemness of glioblastoma stem cells by stabilizing epidermal growth factor receptor variant III.Oncogene · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
DJ-1 (PARK7) is a gene linked to autosomal recessive Parkinson disease (PD). We showed previously that DJ-1 loss sensitizes neurons in models of PD and stroke. However, the biochemical mechanisms underlying this protective role are not completely clear. Here, we identify Von Hippel Lindau (VHL) protein as a critical DJ-1-interacting protein. We provide evidence that DJ-1 negatively regulates VHL ubiquitination activity of the α-subunit of hypoxia-inducible factor-1 (HIF-1α) by inhibiting HIF-VHL interaction. Consistent with this observation, DJ-1 deficiency leads to lowered HIF-1α levels in models of both hypoxia and oxidative stress, two stresses known to stabilize HIF-1α. We also demonstrate that HIF-1α accumulation rescues DJ-1-deficient neurons against 1-methyl-4-phenylpyridinium-induced toxicity. Interestingly, lymphoblast cells extracted from DJ-1-related PD patients show impaired HIF-1α stabilization when compared with normal individuals, indicating that the DJ-1-VHL link may also be relevant to a human context. Together, our findings delineate a model by which DJ-1 mediates neuronal survival by regulation of the VHL-HIF-1α pathway.
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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.