Differential expression of cathepsin X in aging and pathological central nervous system of mice.
Increasing evidence of a fundamental influence of cathepsins on inflammation has drawn interest in a thorough understanding of their role in physiological and pathological processes. Even though the number of identified cathepsins has more than doubled in the last years, information about their expression, regulation and function in the brain is still incomplete. In the present study we analyzed the regional, cellular and subcellular localization and the activity of the recently discovered cathepsin X in the normal, developing and pathological mouse brain. Our results show that CATX is: (i) is expressed in almost all cells in the mouse brain with a preference for glial cells; (ii) already widely expressed early in development and age-dependently upregulated in amount and activity; (iii) prominently localized in the lysosomal system but also scattered in the somal cytoplasm in the aged brain; (iv) upregulated in numerous glial cells of degenerating brain regions in a transgenic mouse model of amyotrophic lateral sclerosis; and (v) associated with plaques in a transgenic mouse model and in Alzheimer patients. These results strongly suggest that cathepsin X is an important player in degenerative processes during normal aging and in pathological conditions.
Wendt
Wiebke
W
Department of Animal Physiology, Ruhr-University of Bochum, D-44780 Bochum, Germany.
Zhu
Xin-Ran
XR
Lübbert
Hermann
H
Stichel
Christine C
CC
D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D053764:Presenilin-1; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D002403:Cathepsins