ArticleProceedings of the National Academy of Sciences of the United States of America2010
Targeting botulinum neurotoxin persistence by the ubiquitin-proteasome system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 97 citations in OpenAlex.
- Botulinum neurotoxin: from molecular pathogenesis to emerging countermeasures.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Characterisation of the SNAP-25 and SNAP-23 cleavage properties of the botulinum neurotoxin-like protein from Enterococcus.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Advances in Clostridial Neurotoxins: Passage of the Intestinal Barrier and Targeting of Specific Neuronal Cells.Toxins · 2026Review
- Phosphorylation of SNAP-25 at Ser187 is enhanced following its cleavage by Botulinum Neurotoxin Serotype A, promoting the dominant-negative effect of the resulting fragment.PLoS pathogens · 2025Article
- Article
- Botulinum Neurotoxins: History, Mechanism, and Applications. A Narrative Review.Journal of neurochemistry · 2025Review
- Unraveling Botulinum Neurotoxin A Light-Chain-Induced Signaling Pathways: A Phosphoproteomic Analysis in a Controlled Cellular Model.International journal of molecular sciences · 2025Article
- Neurotoxin-Derived Optical Probes for Elucidating Molecular and Developmental Biology of Neurons and Synaptic Connections : Toxin-Derived Optical Probes for Neuroimaging.Molecular imaging and biology · 2024Review
- The Degradation of Botulinum Neurotoxin Light Chains Using PROTACs.International journal of molecular sciences · 2024Article
- Review
- Pathogenicity and virulence ofVirulence · 2023Review
- Transformation of a Metal Chelate into a "Catch and Anchor" Inhibitor of Botulinum A Protease.International journal of molecular sciences · 2023Article
- In Silico Conformational Features of Botulinum Toxins A1 and E1 According to Intraluminal Acidification.Toxins · 2022Article
- Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update.Archives of toxicology · 2022Review
- Clostridial Neurotoxins: Structure, Function and Implications to Other Bacterial Toxins.Microorganisms · 2021Review
- A Novel Running Wheel Mouse Model for Botulism and Its Use for the Evaluation of Postsymptom Antitoxin Efficacy.Antimicrobial agents and chemotherapy · 2021Article
- Harnessing the Membrane Translocation Properties of AB Toxins for Therapeutic Applications.Toxins · 2021Review
- Screening of a Focused Ubiquitin-Proteasome Pathway Inhibitor Library Identifies Small Molecules as Novel Modulators of Botulinum Neurotoxin Type A Toxicity.Frontiers in pharmacology · 2021Article
- The mechanisms of action and use of botulinum neurotoxin type A in aesthetics: Key Clinical Postulates II.Journal of cosmetic dermatology · 2020Review
- Two VHH Antibodies Neutralize Botulinum Neurotoxin E1 by Blocking Its Membrane Translocation in Host Cells.Toxins · 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
7 authors at 6 institutions in 1 country.
Funding
Abstract
Botulinum neurotoxins (BoNTs) are the most potent natural toxins known. The effects of BoNT serotype A (BoNT/A) can last several months, whereas the effects of BoNT serotype E (BoNT/E), which shares the same synaptic target, synaptosomal-associated protein 25 (SNAP25), last only several weeks. The long-lasting effects or persistence of BoNT/A, although desirable for therapeutic applications, presents a challenge for medical treatment of BoNT intoxication. Although the mechanisms for BoNT toxicity are well known, little is known about the mechanisms that govern the persistence of the toxins. We show that the recombinant catalytic light chain (LC) of BoNT/E is ubiquitylated and rapidly degraded in cells. In contrast, BoNT/A LC is considerably more stable. Differential susceptibility of the catalytic LCs to ubiquitin-dependent proteolysis therefore might explain the differential persistence of BoNT serotypes. In this regard we show that TRAF2, a RING finger protein implicated in ubiquitylation, selectively associates with BoNT/E LC and promotes its proteasomal degradation. Given these data, we asked whether BoNT/A LC could be targeted for rapid proteasomal degradation by redirecting it to characterized ubiquitin ligase domains. We describe chimeric SNAP25-based ubiquitin ligases that target BoNT/A LC for degradation, reducing its duration in a cellular model for toxin persistence.
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.