ArticleThe Journal of biological chemistry2011
Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses 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
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.Frontiers in physiology · 2020Pooled it
- Inverse relationship between Alzheimer's disease and cancer, and other factors contributing to Alzheimer's disease: a systematic review.BMC neurology · 2016Pooled it
- Genome-Wide CRISPR Screening Identifies Genetic Modulators of Amyloid Precursor Protein Processing.International journal of molecular sciences · 2026Article
- ALS mutations disrupt self-association between the ubiquilin STI1 hydrophobic groove and internal placeholder sequences.The EMBO journal · 2026Article
- Ubiquilin-2 liquid droplets catalyze α-synuclein fibril formation.The EMBO journal · 2025Article
- Ubiquitin-independent proteasomal degradation driven by C-degron pathways.Molecular cell · 2023Article
- Platelet-rich plasma promotes peripheral nerve regeneration after sciatic nerve injury.Neural regeneration research · 2023Article
- One-Step Sortase-Mediated Chemoenzymatic Semisynthesis of Deubiquitinase-Resistant Ub-Peptide Conjugates.ACS omega · 2022Article
- Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential.Acta pharmaceutica Sinica. B · 2022Review
- Analysis of high-risk pedigrees identifies 11 candidate variants for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas.Frontiers in genetics · 2022Article
- Association of the Protein-Quality-Control Protein Ubiquilin-1 With Alzheimer's Disease BothFrontiers in neuroscience · 2022Article
- BET1 variants establish impaired vesicular transport as a cause for muscular dystrophy with epilepsy.EMBO molecular medicine · 2021Article
- ALS/FTD mutations in UBQLN2 are linked to mitochondrial dysfunction through loss-of-function in mitochondrial protein import.Human molecular genetics · 2021Article
- Aggrephagy Deficiency in the Placenta: A New Pathogenesis of Preeclampsia.International journal of molecular sciences · 2021Review
- Remodeling without destruction: non-proteolytic ubiquitin chains in neural function and brain disorders.Molecular psychiatry · 2021Review
- Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery.The Biochemical journal · 2020Review
- ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Unstructured Biology of Proteins from Ubiquitin-Proteasome System: Roles in Cancer and Neurodegenerative Diseases.Biomolecules · 2020Article
- The cellular expression and proteolytic processing of the amyloid precursor protein is independent of TDP-43.Bioscience reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer disease (AD) is associated with extracellular deposition of proteolytic fragments of amyloid precursor protein (APP). Although mutations in APP and proteases that mediate its processing are known to result in familial, early onset forms of AD, the mechanisms underlying the more common sporadic, yet genetically complex forms of the disease are still unclear. Four single-nucleotide polymorphisms within the ubiquilin-1 gene have been shown to be genetically associated with AD, implicating its gene product in the pathogenesis of late onset AD. However, genetic linkage between ubiquilin-1 and AD has not been confirmed in studies examining different populations. Here we show that regardless of genotype, ubiquilin-1 protein levels are significantly decreased in late onset AD patient brains, suggesting that diminished ubiquilin function may be a common denominator in AD progression. Our interrogation of putative ubiquilin-1 activities based on sequence similarities to proteins involved in cellular quality control showed that ubiquilin-1 can be biochemically defined as a bona fide molecular chaperone and that this activity is capable of preventing the aggregation of amyloid precursor protein both in vitro and in live neurons. Furthermore, we show that reduced activity of ubiquilin-1 results in augmented production of pathogenic amyloid precursor protein fragments as well as increased neuronal death. Our results support the notion that ubiquilin-1 chaperone activity is necessary to regulate the production of APP and its fragments and that diminished ubiquilin-1 levels may contribute to AD pathogenesis.
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.