ArticlePloS one2014
Phosphorylation of mutant huntingtin at serine 116 modulates neuronal toxicity.
Article in PloS one, 2014. 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
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
28 citing papers in PubMed, 52 citations in OpenAlex.
- Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington's Disease.Molecular neurobiology · 2025Article
- Post-Translational Modifications of Huntingtin: Mechanistic Insights and Therapeutic Opportunities in Huntington's Disease.International journal of molecular sciences · 2025Review
- Huntingtin inclusion bodies have distinct immunophenotypes and ubiquitination profiles in the Huntington's disease human cerebral cortex.Scientific reports · 2025Article
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- The HSPB1-p62/SQSTM1 functional complex regulates the unconventional secretion and transcellular spreading of the HD-associated mutant huntingtin protein.Human molecular genetics · 2023Article
- Full-length huntingtin is palmitoylated at multiple sites and post-translationally myristoylated following caspase-cleavage.Frontiers in physiology · 2023Article
- Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington's Disease.Biomedicines · 2022Review
- pS421 huntingtin modulates mitochondrial phenotypes and confers neuroprotection in an HD hiPSC model.Cell death & disease · 2020Article
- How Do Post-Translational Modifications Influence the Pathomechanistic Landscape of Huntington's Disease? A Comprehensive Review.International journal of molecular sciences · 2020Review
- G2019S-LRRK2 mutation enhances MPTP-linked Parkinsonism in mice.Human molecular genetics · 2020Article
- Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor.Neurobiology of disease · 2019Article
- Hdac4 Interactions in Huntington's Disease Viewed Through the Prism of Multiomics.Molecular & cellular proteomics : MCP · 2019Article
- Design and characterization of mutant and wildtype huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.The Journal of biological chemistry · 2019Article
- Cysteamine Protects Neurons from Mutant Huntingtin Toxicity.Journal of Huntington's disease · 2019Article
- Therapeutic approaches to Huntington disease: from the bench to the clinic.Nature reviews. Drug discovery · 2018Review
- N6-Furfuryladenine is protective in Huntington's disease models by signaling huntingtin phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- PPARδ activation by bexarotene promotes neuroprotection by restoring bioenergetic and quality control homeostasis.Science translational medicine · 2017Article
- Post-translational modifications clustering within proteolytic domains decrease mutant huntingtin toxicity.The Journal of biological chemistry · 2017Article
- Post-Translational Modifications (PTMs), Identified on Endogenous Huntingtin, Cluster within Proteolytic Domains between HEAT Repeats.Journal of proteome research · 2017Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphorylation has been shown to have a significant impact on expanded huntingtin-mediated cellular toxicity. Several phosphorylation sites have been identified on the huntingtin (Htt) protein. To find new potential therapeutic targets for Huntington's Disease (HD), we used mass spectrometry to identify novel phosphorylation sites on N-terminal Htt, expressed in HEK293 cells. Using site-directed mutagenesis we introduced alterations of phosphorylation sites in a N586 Htt construct containing 82 polyglutamine repeats. The effects of these alterations on expanded Htt toxicity were evaluated in primary neurons using a nuclear condensation assay and a direct time-lapse imaging of neuronal death. As a result of these studies, we identified several novel phosphorylation sites, validated several known sites, and discovered one phospho-null alteration, S116A, that had a protective effect against expanded polyglutamine-mediated cellular toxicity. The results suggest that S116 is a potential therapeutic target, and indicate that our screening method is useful for identifying candidate phosphorylation sites.
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.