Transglutaminase 2 exacerbates α-synuclein toxicity in mice and yeast.

ABSTRACT: α-Synuclein is a key pathogenic protein that aggregates in hallmark lesions in Parkinson's disease and other α-synucleinopathies. Prior in vitro studies demonstrated that it is a substrate for cross-linking by transglutaminase 2 (TG2) into higher-order species. Here we investigated whether this increased aggregation occurs in vivo and whether TG2 exacerbates α-synuclein toxicity in Mus musculus and Saccharomyces cerevisiae. Compared with α-synuclein transgenic (Syn(Tg)) mice, animals double transgenic for human α-synuclein and TG2 (TG2(Tg)/Syn(Tg)) manifested greater high-molecular-weight insoluble species of α-synuclein in brain lysates and developed α-synuclein aggregates in the synaptic vesicle fraction. In addition, larger proteinase K-resistant aggregates developed, along with increas

SUBMITTER: Grosso H 

PROVIDER: S-EPMC4202112 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature