ArticleScience advances2022
Deubiquitinase CYLD acts as a negative regulator of dopamine neuron survival in Parkinson's disease.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- The ubiquitin-proteasome system and proteostasis in the cochlea and sensorineural hearing disorders.Molecular biomedicine · 2026Review
- Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.Neural regeneration research · 2026Article
- Inhibition of YTHDF2-mediated CYLD mRNA degradation promotes neuronal ferroptosis and pain in Parkinson's disease through NOX4 deubiquitination.Cell biology and toxicology · 2026Article
- Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes.EMBO reports · 2026Article
- Plant natural products targeting NLRP3 inflammasome in Parkinson's disease: Molecular activation and regulation to therapeutics.iScience · 2026Review
- Mitophagy: A key regulator in the pathophysiology and treatment of spinal cord injury.Neural regeneration research · 2026Article
- Mitochondrial echoes in the bloodstream: decoding ccf-mtDNA for the early detection and prognosis of hepatocellular carcinoma.Cell & bioscience · 2025Review
- Genetic variants ofIBRO neuroscience reports · 2025Article
- USP14 inhibits mitophagy and promotes tumorigenesis and chemosensitivity through deubiquitinating BAG4 in microsatellite instability-high colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Role of CYLD in brain physiology and pathology.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology.Pharmacological research · 2024Review
- Bioactivated Glucoraphanin Modulates Genes Involved in Necroptosis on Motor-Neuron-like Nsc-34: A Transcriptomic Study.Antioxidants (Basel, Switzerland) · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.Cancers · 2023Article
- The mitophagy pathway and its implications in human diseases.Signal transduction and targeted therapy · 2023Review
- CYLD in health and disease.Disease models & mechanisms · 2023Review
- The Potential of Cylindromatosis (CYLD) as a Therapeutic Target in Oxidative Stress-Associated Pathologies: A Comprehensive Evaluation.International journal of molecular sciences · 2023Review
- Cell Biology of Parkin: Clues to the Development of New Therapeutics for Parkinson's Disease.CNS drugs · 2022Review
- Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease.Neuron · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in PINK1 and parkin highlight the mitochondrial axis of Parkinson's disease (PD) pathogenesis. PINK1/parkin regulation of the transcriptional repressor PARIS bears direct relevance to dopamine neuron survival through augmentation of PGC-1α-dependent mitochondrial biogenesis. Notably, knockout of PARIS attenuates dopaminergic neurodegeneration in mouse models, indicating that interventions that prevent dopaminergic accumulation of PARIS could have therapeutic potential in PD. To this end, we have identified the deubiquitinase cylindromatosis (CYLD) to be a regulator of PARIS protein stability and proteasomal degradation via the PINK1/parkin pathway. Knockdown of CYLD in multiple models of PINK1 or parkin inactivation attenuates PARIS accumulation by modulating its ubiquitination levels and relieving its repressive effect on PGC-1α to promote mitochondrial biogenesis. Together, our studies identify CYLD as a negative regulator of dopamine neuron survival, and inhibition of CYLD may potentially be beneficial in PD by lowering PARIS levels and promoting mitochondrial biogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.