Distribution of tripeptidyl peptidase I in human tissues under normal and pathological conditions

Tripeptidyl peptidase I (TPP I) is a lysosomal exopeptidase that cleaves tr ipeptides from the free N-termini of oligopeptides. Mutations in this enzym e are associated with the classic late-infantile form of neuronal ceroid li pofuscinosis (CLN2), an autosomal recessive disorder leading to severe brai n damage. To gain more insight into CLN2 pathogenesis and the role of TPP I in human tissues in general, we analyzed the temporal and spatial distribu tion of TPP I in the brain and its localization in internal organs under no rmal and pathological conditions. We report that TPP I immunoreactivity app ears in neurons late in gestation and increases gradually in the postnatal period, matching significantly the final differentiation and maturation of neural tissue. Endothelial cells, choroid plexus, microglial cells, and epe ndyma showed TPP I immunostaining distinctly earlier than neurons. Acquisit ion of the adult pattern of TPP I distribution in the brain at around the a ge of 2 years correlates with the onset of clinical signs in CLN2 subjects. In adults, TPP I was found in an types of cells in the brain and internal organs we studied, although the intensity of TPP I labeling varied among se veral types of cells and showed a noticeable predilection for cells and/or organs associated with peptide hormone and neuropeptide production. In addi tion, TPP I immunoreactivity was increased in aging brain, neurodegenerativ e and lysosomal storage disorders, and some differentiated neoplasms and wa s reduced in ischemic/anoxic areas and undifferentiated tumors. These findi ngs suggest that TPP I is involved in general protein turnover and that its expression may be controlled by various regulatory mechanisms, which highl ights the importance of this enzyme for normal function of cells and organs in humans.