ArticleiScience2022
Discovery of small-molecule positive allosteric modulators of Parkin E3 ligase.
Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
The trial behind it
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
28 citing papers in PubMed, 34 citations in OpenAlex.
- Cell-Type-Specific Calibration of Mitochondrial Ubiquitination in Stem Cell Fate Decisions.Stem cell reviews and reports · 2026Review
- Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026Review
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- Alternative Translation Initiation in PRKN Delays the Onset of Parkinson's Disease and Offers a Therapeutic Target.Annals of neurology · 2026Article
- The role of phospho-ubiquitin in mitochondrial health and diseases.The Journal of biological chemistry · 2026Review
- Neural cell state modulation bybioRxiv : the preprint server for biology · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- E3 ubiquitin ligases in neurodegenerative diseases.Military Medical Research · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Versatile roles of inositol hexakisphosphate in the ubiquitin-proteasome system.Essays in biochemistry · 2025Review
- Activation of endogenous PRKN by structural derepression is linked to increased turnover of the E3 ubiquitin ligase.Autophagy · 2025Article
- Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.Biochemical Society transactions · 2025Review
- Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress.Science advances · 2025Article
- Stressful situations: Molecular insights on mitochondrial quality control pathways.The Journal of biological chemistry · 2025Review
- Mitophagy's impacts on cancer and neurodegenerative diseases: implications for future therapies.Journal of hematology & oncology · 2025Review
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- The role of PINK1-Parkin in mitochondrial quality control.Nature cell biology · 2024Review
- Activation of parkin by a molecular glue.Nature communications · 2024Article
- Naturally occurring hyperactive variants of human parkin.Communications biology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacological activation of the E3 ligase Parkin represents a rational therapeutic intervention for the treatment of Parkinson's disease. Here we identify several compounds that enhance the activity of wildtype Parkin in the presence of phospho-ubiquitin and act as positive allosteric modulators (PAMs). While these compounds activate Parkin in a series of biochemical assays, they do not act by thermally destabilizing Parkin and fail to enhance the Parkin translocation rate to mitochondria or to enact mitophagy in cell-based assays. We conclude that in the context of the cellular milieu the therapeutic window to pharmacologically activate Parkin is very narrow.
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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.