Tissue transglutaminase is not involved in the aggregate formation of stably expressed α-synuclein in SH-SY5Y human neuroblastoma cells

Intraneuronal deposition containing alpha-synuclein is implicated in the pathogenesis of synucleinopathies including Parkinsons disease (PD). Although it has been demonstrated that cytoplasmic inclusions of wild type alpha-synuclein are observed in the brain of PD patients and that alpha-synuclein mutations such as A30P and A53T accelerate aggregate formation, the exact mechanism by which alpha-synuclein forms insoluble aggregates is still controversial. In the present study, to understand the possible involvement of tissue transglutaminase (tTG) in aggregate formation of alpha-synuclein, SH-SY5Y cell lines stably expressing wild type or mutant (A30P or A53T) alpha-synuclein were created and aggregate formation of alpha-synuclein was observed upon activation of tTG. The data demonstrated that alpha-synuclein negligibly interacted with tTG and that activation of tTG did not result in the aggregate formation of alpha-synuclein in SH-SY5Y cells overexpressing either wild type or mutant alpha-synuclein. In addition, alpha-synuclein was not modified by activated tTG in situ. These data suggest that tTG is unlikely to be a contributing factor to the formation of aggregates of alpha-synuclein in a stable cell model.