ArticleOncotarget2016
Loss of NEDD4 contributes to RTP801 elevation and neuron toxicity: implications for Parkinson's disease.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- MPTP and rotenone cause dopaminergic neuronal death by increasing DDIT4 promoter lactylation.Acta pharmacologica Sinica · 2026Article
- E3 ubiquitin ligase NEDD4 inhibits PEDV infection through ubiquitination and degradation of the viral primase NSP8.Journal of virology · 2026Article
- Understanding the Pre-Clinical Stages of Parkinson's Disease: Where Are We in Clinical and Research Settings?International journal of molecular sciences · 2025Review
- RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.Nucleic acids research · 2024Article
- Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- DMT1 ubiquitination by Nedd4 protects against ferroptosis after intracerebral hemorrhage.CNS neuroscience & therapeutics · 2024Article
- p21-activated kinase 4 controls the aggregation of α-synuclein by reducing the monomeric and aggregated forms of α-synuclein: involvement of the E3 ubiquitin ligase NEDD4-1.Cell death & disease · 2022Article
- The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2022Review
- Atypical Ubiquitination and Parkinson's Disease.International journal of molecular sciences · 2022Review
- Review
- DDIT4 S-Nitrosylation Aids p38-MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Deletion of ubiquitin ligase Nedd4l exacerbates ischemic brain damage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Exploration of Aberrant E3 Ligases Implicated in Alzheimer's Disease and Development of Chemical Tools to Modulate Their Function.Frontiers in cellular neuroscience · 2021Review
- Synaptic RTP801 contributes to motor-learning dysfunction in Huntington's disease.Cell death & disease · 2020Article
- Functional role of WW domain-containing proteins in tumor biology and diseases: Insight into the role in ubiquitin-proteasome system.FASEB bioAdvances · 2020Article
- Association between polymorphism of the NEDD4 gene and cognitive dysfunction of schizophrenia patients in Chinese Han population.BMC psychiatry · 2019Article
- [Neuroprotective effect of rapamycin against Parkinson's disease in mice].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2018Article
- Intracellular and Intercellular Signalling Mechanisms following DNA Damage Are Modulated By PINK1.Oxidative medicine and cellular longevity · 2018Article
- Amyloid-β Induces AMPA Receptor Ubiquitination and Degradation in Primary Neurons and Human Brains of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a disorder characterized by the degeneration of certain neuronal populations in the central and peripheral nervous system. One of the hallmarks of the disease is the toxic accumulation of proteins within susceptible neurons due to major impairment in the degradation/clearance protein systems.RTP801 is a pro-apoptotic protein that is sufficient and necessary to induce neuronal death in cellular and animal models of PD. RTP801 is also upregulated in sporadic and parkin mutant PD brains. Here, we report the role of NEDD4, an E3 ligase involved in α-synuclein degradation and PD pathogenesis, in the regulation of RTP801 protein levels and toxicity. NEDD4 polyubiquitinates RTP801 in a cell-free system and in cellular cultures, and they interact physically. NEDD4 conjugates K63-ubiquitin chains to RTP801 and targets it for degradation. NEDD4 regulates RTP801 protein levels in both cultured cells and in the brain tissue. NEDD4 levels are diminished in nigral neurons from human PD brains. Interestingly, neurotoxin 6-OHDA decreases dramatically NEDD4 protein expression but elevates RTP801 protein levels. Moreover, NEDD4 protects neuronal PC12 cells from both 6-OHDA and RTP801-induced toxicity. In primary cortical neurons, NEDD4 knockdown toxicity is mediated by RTP801 since the double knockdown of RTP801 and NEDD4 abrogates the loss of phospho Ser473-Akt and the appearance of caspase-cleaved spectrin fragments.Thus, NEDD4 ligase regulates RTP801 and is sensitive to PD-associated oxidative stress. This suggests that NEDD4 loss of function in PD could contribute importantly into neuronal death by elevating RTP801.
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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.