ArticleHuman molecular genetics2016
PINK1 and Parkin are genetic modifiers for FUS-induced neurodegeneration.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- From Cell Architecture to Mitochondrial Signaling: Role of Intermediate Filaments in Health, Aging, and Disease.International journal of molecular sciences · 2025Review
- Review
- Regulation of DNA damage response by RNA/DNA-binding proteins: Implications for neurological disorders and aging.Ageing research reviews · 2024Review
- Conformational change of RNA-helicase DHX30 by ALS/FTD-linked FUS induces mitochondrial dysfunction and cytosolic aggregates.Scientific reports · 2022Article
- A hidden layer of structural variation in transposable elements reveals potential genetic modifiers in human disease-risk loci.Genome research · 2022Article
- Mechanistic Insights of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis: An Update on a Lasting Relationship.Metabolites · 2022Review
- Mitophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention.Oxidative medicine and cellular longevity · 2022Review
- New perspectives on cytoskeletal dysregulation and mitochondrial mislocalization in amyotrophic lateral sclerosis.Translational neurodegeneration · 2021Review
- TDP-43 and PINK1 mediate CHCHD10Nature communications · 2021Article
- Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021Review
- Mitophagy Modulation, a New Player in the Race against ALS.International journal of molecular sciences · 2021Review
- Mitochondrial Quality Control Strategies: Potential Therapeutic Targets for Neurodegenerative Diseases?Frontiers in neuroscience · 2021Review
- The multifaceted role of kinases in amyotrophic lateral sclerosis: genetic, pathological and therapeutic implications.Brain : a journal of neurology · 2020Review
- RNA-Binding Proteins Implicated in Mitochondrial Damage and Mitophagy.Frontiers in cell and developmental biology · 2020Review
- Neuroprotective Role of GLP-1 Analog for Retinal Ganglion Cells via PINK1/Parkin-Mediated Mitophagy in Diabetic Retinopathy.Frontiers in pharmacology · 2020Article
- Mitochondrial transport serves as a mitochondrial quality control strategy in axons: Implications for central nervous system disorders.CNS neuroscience & therapeutics · 2019Review
- Novel and Recurrent Mutations in a Cohort of Chinese Patients With Young-Onset Amyotrophic Lateral Sclerosis.Frontiers in neuroscience · 2019Article
- FUS-induced neurotoxicity in Drosophila is prevented by downregulating nucleocytoplasmic transport proteins.Human molecular genetics · 2018Article
- Amyotrophic Lateral Sclerosis associated FUS mutation shortens mitochondria and induces neurotoxicity.Scientific reports · 2018Article
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 6 institutions in 2 countries.
Funding
Abstract
Dysregulation of Fused in Sarcoma (FUS) gene expression is associated with fronto-temporal lobar degeneration (FTLD), and missense mutations in the FUS gene have been identified in patients affected by amyotrophic lateral sclerosis (ALS). However, molecular and cellular defects underlying FUS proteinopathy remain to be elucidated. Here, we examined whether genes important for mitochondrial quality control play a role in FUS proteinopathy. In our genetic screening, Pink1 and Park genes were identified as modifiers of neurodegeneration phenotypes induced by wild type (Wt) or ALS-associated P525L-mutant human FUS. Down-regulating expression of either Pink1 or Parkin genes ameliorated FUS-induced neurodegeneration phenotypes. The protein levels of PINK1 and Parkin were elevated in cells overexpressing FUS. Remarkably, ubiquitinylation of Miro1 protein, a downstream target of the E3 ligase activity of Parkin, was also increased in cells overexpressing FUS protein. In fly motor neurons expressing FUS, both motility and processivity of mitochondrial axonal transport were reduced by expression of either Wt- or P525L-mutant FUS. Finally, down-regulating PINK1 or Parkin partially rescued the locomotive defects and enhanced the survival rate in transgenic flies expressing FUS. Our data indicate that PINK1 and Parkin play an important role in FUS-induced neurodegeneration. This study has uncovered a previously unknown link between FUS proteinopathy and PINK1/Parkin genes, providing new insights into the pathogenesis of FUS proteinopathy.
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.