Expression of tissue transglutaminase, an enzyme involved in a-synuclein aggregation, is increased in the Caudate Putamen complex of Parkinsonian patients

In Parkinson's disease, increased tissue transglutaminase activity is hypothesized to be involved in the pathological aggregation of the protein a-synuclein. a-Synuclein is highly expressed in the nigral dopaminergic nerve fibers that project into the Caudate Putamen complex. Hence, altered levels of tissue transglutaminase expression in the Caudate Putamen could have a large impact on a-synuclein function. The present study shows the localization of tissue transglutaminase protein in presynaptic fibers of the Caudate Putamen and its increased expression in Parkinsonian patients as compared to age-matched controls. Based on these results, it is concluded that upregulation of tissue transglutaminase occurs in Parkinson's disease at the level of presynaptic input to the Caudate Putamen, which may have serious consequences for the proper function of presynaptic proteins, like a-synuclein.