ArticleNeuroscience2020
Enhanced Susceptibility of PINK1 Knockout Rats to α-Synuclein Fibrils.
Article in Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Rethinking 'rare'Journal of Parkinson's disease · 2025Pooled it
- Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026Review
- Cardiolipin and mitochondrial membrane integrity in neurodegeneration: insights from α-synuclein-driven Parkinson's disease.Acta neuropathologica communications · 2025Review
- Review
- PINK1 deficiency permits the development of Lewy body dementia with coexisting Aβ pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.Behavioral and brain functions : BBF · 2025Review
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Liquid-liquid phase separation and conformational strains ofFrontiers in molecular neuroscience · 2024Review
- Knockout or inhibition of USP30 protects dopaminergic neurons in a Parkinson's disease mouse model.Nature communications · 2023Article
- Alpha-synuclein-associated changes in PINK1-PRKN-mediated mitophagy are disease context dependent.Brain pathology (Zurich, Switzerland) · 2023Article
- Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights intoZoological research · 2023Review
- Leveraging the preformed fibril model to distinguish between alpha-synuclein inclusion- and nigrostriatal degeneration-associated immunogenicity.Neurobiology of disease · 2022Review
- Analysis of hemisphere-dependent effects of unilateral intrastriatal injection of α-synuclein pre-formed fibrils on mitochondrial protein levels, dynamics, and function.Acta neuropathologica communications · 2022Article
- PTEN-Induced Putative Kinase 1 Dysfunction Accelerates Synucleinopathy.Journal of Parkinson's disease · 2022Article
- Peiminine Reduces ARTS-Mediated Degradation of XIAP by Modulating the PINK1/Parkin Pathway to Ameliorate 6-Hydroxydopamine Toxicity and α-Synuclein Accumulation in Parkinson's Disease Models In Vivo and In Vitro.International journal of molecular sciences · 2021Article
- Roles of physical exercise in neurodegeneration: reversal of epigenetic clock.Translational neurodegeneration · 2021Review
- Targeting PINK1 Using Natural Products for the Treatment of Human Diseases.BioMed research international · 2021Review
- Review
- Targeting mitophagy in Parkinson's disease.The Journal of biological chemistryReview
- A Summary of Phenotypes Observed in the In Vivo Rodent Alpha-Synuclein Preformed Fibril Model.Journal of Parkinson's diseaseReview
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The main neuropathological hallmarks of Parkinson's disease (PD) are loss of dopaminergic neurons in the substantia nigra and intraneuronal protein aggregates immunoreactive for α-synuclein phosphorylated at serine 129 (pS129). Most cases of PD are idiopathic; however, genetic mutations have been identified in several genes linked to familial PD. Mutations in the gene encoding α-synuclein are causally linked to dominantly inherited forms of PD and mutations in the PTEN-induced kinase-1 (PINK1) gene are linked to recessively inherited forms of PD. Because abnormal α-synuclein protein aggregates appear spontaneously in PINK1 knockout (KO) rats, we hypothesize that PINK1-deficiency causes endogenous α-synuclein to be more prone to aggregation. α-Synuclein aggregation does not normally occur in mice or rats, however, it can be induced by intracranial injection of α-synuclein pre-formed fibrils (PFFs), which also induces loss of dopaminergic nigral neurons 3-6 months post-injection. Because PINK1-deficiency is linked to early-onset PD, we further hypothesize that PINK1 KO rats will show earlier PFF-induced neurodegeneration compared to wild-type (WT) rats. Herein, we report that intracranial injection of α-synuclein PFFs into the dorsal striatum induced more abundant pS129 α-synuclein in PINK1 KO rat brains compared to WT littermate controls. Moreover, the synuclein extracted from the brains of PFF-injected PINK1 KO rats was more insoluble compared to PFF-injected WT littermates, suggesting greater progression of α-synuclein pathology in PINK1 KO rats. Four weeks post-injection, PFFs caused significant loss of dopaminergic neurons in the substantia nigra of PINK1 KO rats, but not WT controls. Together, our results indicate that PINK1 deficiency increases vulnerability to α-synuclein aggregation and dopaminergic neurodegeneration in vivo.
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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.