ArticleMolecular neurobiology2018
6-OHDA Induces Oxidation of F-box Protein Fbw7β by Chaperone-Mediated Autophagy in Parkinson's Model.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapy.Molecular and cellular biochemistry · 2023Review
- Activation of GRP78 ATPase suppresses A549 lung cancer cell migration by promoting ITGB4 degradation.Cell adhesion & migration · 2022Article
- Parkinson's Disease Master Regulators on Substantia Nigra and Frontal Cortex and Their Use for Drug Repositioning.Molecular neurobiology · 2021Article
- Implications of FBXW7 in Neurodevelopment and Neurodegeneration: Molecular Mechanisms and Therapeutic Potential.Frontiers in cellular neuroscience · 2021Review
- The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson's Disease.Frontiers in aging neuroscience · 2021Review
- Isoforms of RNF128 Regulate the Stability of Mutant P53 in Barrett's Esophageal Cells.Gastroenterology · 2020Article
- Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma.Frontiers in aging neuroscience · 2020Article
- Recent progress in the role of autophagy in neurological diseases.Cell stress · 2019Review
- Malfunctioning of Chaperone-Mediated Autophagy in Parkinson's Disease: Feats, Constraints, and Flaws of Modulators.Neurotoxicity research · 2019Review
- Targeting Chaperone-Mediated Autophagy for Disease Therapy.Current pharmacology reports · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Parkinson's disease (PD) is the most common movement disorder disease, and its pathological feature is the degenerative loss of dopaminergic neurons in the substantia nigra compacta (SNc). In this study, we investigated whether distinct stress conditions target F-box protein Fbw7β via converging mechanisms. Our results showed that the 6-hyroxydopamine (6-OHDA), which causes PD in animals' models, led to decreased stability of Fbw7β in DA neuronal SN4741 cells. Further experiments suggested that oxidized Fbw7β bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity. Oxidative stress also increased the level of lysosomal-associated membrane protein 2A (LAMP2A), the rate-limiting receptor for CMA substrate flux, and stimulated CMA activity. These changes resulted in accelerated degradation of Fbw7β. 6-OHDA induced Fbw7β oxidation and increased LAMP2A in the SNc region of the mouse models. Consistently, the levels of oxidized Fbw7β were higher in postmortem PD brains compared with the controls. These findings for the first time revealed the specific mechanism of ubiquitin ligases, oxidative stress, and CMA-mediated protein degradation, to provide a new theoretical basis for further clarifying the mechanism of PD.
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