ArticleProceedings of the National Academy of Sciences of the United States of America2026
The cross-linking activity of transglutaminase 2 drives α-Synuclein pathology in synucleinopathy models.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- Transcriptomic Challenges We Faced with Animal Models for Neurological Disorders.Current issues in molecular biology · 2026Review
- The cross-linking activity of transglutaminase 2 drives α-Synuclein pathology in synucleinopathy models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Transglutaminase 2 (TG2) is implicated in synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies, as it promotes α-Synuclein (α-Syn) aggregation in vitro, and evidence for its activity is detected in Lewy bodies in human postmortem brains. Additionally, TG2 overexpression exacerbates α-Syn toxicity in double transgenic mice, while TG2 deletion mitigates the phenotype of α-Syn transgenic mice. Considering that TG2 is a multidomain and multifunctional protein, the present study was carried out to confirm that the transamidase activity of TG2 specifically drives its pathogenetic role in synucleinopathies. We generated transgenic mice expressing a catalytically inactive W241A mutant TG2 and compared them with TG2-overexpressing and TG2 knockout mice using the α-Syn preformed fibril (PFF) model. We also examined double transgenic mice coexpressing human α-Syn with either wild-type TG2 or mutant TG2, alongside α-Syn single transgenic controls. 6 mo post-PFF injection, or at 6 mo of age in the double transgenic lines, the exacerbation of the behavioral and neuropathological phenotype seen with TG2 overexpression was lost with mutant TG2 overexpression in both models. Parallel findings were replicated in PD patient induced pluripotent stem cell-derived dopaminergic neurons. These findings indicate that the cross-linking activity of TG2 plays a pivotal role in α-Syn aggregation and toxicity, underscoring its significance as a therapeutic target in synucleinopathies.
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.