The cross-linking activity of transglutaminase 2 drives α-Synuclein pathology in synucleinopathy models - PubMed
5 hours ago
- #Parkinson’s disease
- #α-Synuclein
- #transglutaminase 2
- Transglutaminase 2 (TG2) is implicated in synucleinopathies like Parkinson's disease (PD) and dementia with Lewy bodies.
- TG2 promotes α-Synuclein (α-Syn) aggregation in vitro and is detected in Lewy bodies in human postmortem brains.
- TG2 overexpression exacerbates α-Syn toxicity in mice, while TG2 deletion mitigates the phenotype in α-Syn transgenic mice.
- A study confirmed that the transamidase activity of TG2 specifically drives its pathogenetic role in synucleinopathies.
- Transgenic mice expressing a catalytically inactive W241A mutant TG2 showed no exacerbation of behavioral and neuropathological phenotypes seen with TG2 overexpression.
- Similar findings were replicated in PD patient induced pluripotent stem cell-derived dopaminergic neurons.
- The cross-linking activity of TG2 plays a pivotal role in α-Syn aggregation and toxicity, making it a significant therapeutic target in synucleinopathies.