Upregulation of cathepsin S in the aging and pathological nervous system of mice.

Cathepsins have long been regarded enzymes that are primarily involved in general protein turnover within lysosomes. However, more recently, their differential cell and tissue distributions suggest that at least some of them participate in specific cellular processes. Cathepsin S (CATS) is mainly expressed in cells of mononuclear phagocytotic origin and plays a major role in the MHC-II-mediated antigen presentation. Although a central role for CATS in brain function has also been suggested, its localization and regulation in the central nervous system are still poorly understood. In the present study we investigated the regional and cellular expression of CATS in normal, aging and pathological mouse brain. Our studies show that CATS is expressed throughout the adult mouse brain, in particular in microglial cells. In aged mice, CATS protein expression increases in these cells. In addition, it became apparent that in old mice a larger number of neuronal cells stained positive for this protease. At the subcellular level, CATS immunostaining accumulated in granules, indicating a lysosomal localization. In a transgenic mouse model of amyotrophic lateral sclerosis expressing mutant superoxide dismutase 1 (SOD1), CATS transcript and protein levels were significantly upregulated in spinal cord and lower brain regions displaying neuronal degeneration. The majority of strongly immunopositive cells in these regions exhibited microglial morphology. These results suggest that CATS participates in inflammatory processes accompanying aging and pathologies of the CNS.