ArticleNeuroscience2013
Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease.
Article in Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- High molecular weight insoluble parkin in the substantia nigra of patients with idiopathic Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Neural cell state modulation bybioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of exercise-induced neuroprotection against Parkinson's disease.Sports medicine and health science · 2026Review
- Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.Autophagy · 2025Article
- Carnosic Acid Attenuated the Motor Impairment by Bisphenol A is Related to the Regulation of Autophagy Through Parkin in In Vitro and In Vivo.Molecular neurobiology · 2025Article
- Rotenone Exposure During Development Conditions Parkinsonian Phenotype in Young Adult Rats.Toxics · 2025Article
- Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson's Disease.International journal of molecular sciences · 2024Review
- Biochemical study of the effect of mesenchymal stem cells-derived exosome versus L-Dopa in experimentally induced Parkinson's disease in rats.Molecular and cellular biochemistry · 2023Article
- Role of dopamine in the pathophysiology of Parkinson's disease.Translational neurodegeneration · 2023Review
- Parkinson's disease neurons exhibit alterations in mitochondrial quality control proteins.NPJ Parkinson's disease · 2023Article
- Mitochondrial Hydrogen Peroxide Activates PTEN and Inactivates Akt Leading to Autophagy Inhibition-Dependent Cell Death in Neuronal Models of Parkinson's Disease.Molecular neurobiology · 2023Article
- Selective dopaminergic vulnerability in Parkinson's disease: new insights into the role of DAT.Frontiers in neuroscience · 2023Review
- Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients.Metabolites · 2022Article
- Cell Biology of Parkin: Clues to the Development of New Therapeutics for Parkinson's Disease.CNS drugs · 2022Review
- A Balance Between Autophagy and Other Cell Death Modalities in Cancer.Methods in molecular biology (Clifton, N.J.) · 2022Article
- CSF MicroRNAs Reveal Impairment of Angiogenesis and Autophagy in Parkinson Disease.Neurology. Genetics · 2021Article
- Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.Autophagy · 2021Review
- Multitasking guardian of mitochondrial quality: Parkin function and Parkinson's disease.Translational neurodegeneration · 2021Review
- Genetic Imaging of Neuroinflammation in Parkinson's Disease: Recent Advancements.Frontiers in cell and developmental biology · 2021Review
- Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases.Human molecular genetics · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is a motor disorder that involves death of dopaminergic neurons in the substantia nigra pars compacta. Parkin is an autosomal recessive gene that is mutated in early onset PD. We investigated the role of parkin and autophagic clearance in postmortem nigrostriatal tissues from 22 non-familial sporadic PD patients and 15 control samples. Parkin was insoluble with altered cytosolic expression in the nigrostriatum of sporadic PD. Parkin insolubility was associated with lack of degradation of ubiquitinated proteins and accumulation of α-Synuclein and parkin in autophagosomes, suggesting autophagic defects in PD. To test parkin's role in mediating autophagic clearance, we used lentiviral gene transfer to express human wild type or mutant parkin (T240R) with α-Synuclein in the rat striatum. Lentiviral expression of α-Synuclein led to accumulation of autophagic vacuoles, while co-expression of parkin with α-Synuclein facilitated autophagic clearance. Subcellular fractionation showed accumulation of α-Synuclein and tau hyper-phosphorylation (p-Tau) in autophagosomes in gene transfer models, similar to the effects observed in PD brains, but parkin expression led to protein deposition into lysosomes. However, parkin loss of function mutation did not affect autophagic clearance. Taken together, these data suggest that functional parkin regulates autophagosome clearance, while decreased parkin solubility may alter normal autophagy in sporadic PD.
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