Document Information


PMID 17306794  (  )
Title Differential expression of cathepsin X in aging and pathological central nervous system of mice.
Abstract 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. Bochum, Germany.

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Targets by SciMiner Summary

HUGO ID Symbol Target Name #Occur ActualStr
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)17APP | amyloid | amyloid beta protein |
9508PSEN1presenilin 1 (Alzheimer disease 3)14PS1 | presenilin 1 |
2527CTSBcathepsin B9cathepsin b | CATB |
2537CTSL1cathepsin L15cathepsin l | CATL |
6149ITGAMintegrin, alpha M (complement component 3 receptor 3 subunit)4CD11b |
4235GFAPglial fibrillary acidic protein4glial fibrillary acidic protein | GFAP |
2536CTSKcathepsin K4cathepsin x |
1509CASP8caspase 8, apoptosis-related cysteine peptidase3cysteine protease |
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))2SOD1 |
10417RPS27Aribosomal protein S27a1ubiquitin |
2545CTSScathepsin S1cathepsin s |
11801THY1Thy-1 cell surface antigen1Thy1 |
3146ECE1endothelin converting enzyme 11ECE-1 |
7762NEUROD1neurogenic differentiation 11beta2 |
2530CTSEcathepsin E1CATE |

 


Targets by SciMiner Full list

HUGO ID Symbol Name ActualStr Score FlankingText
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6SOD1-G93A and the Alzheimer's disease double transgenic mouse model APP/PS1 APP PS1
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9and the Alzheimer's disease double transgenic mouse model APP/PS1 APP PS1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD12.4copies ( Gurney et al. 1994 of the human mutant SOD1 gene (Cu/Zn-SOD) Cu Zn-SOD containing the Gly 93 _amp_#x2192 Ala
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)amyloid1.3Transgenic mice expressing the human amyloid precursor protein (APP) APP with the Swedish mutation (K670M/N671L) K670M
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6Transgenic mice expressing the human amyloid precursor protein (APP) APP with the Swedish mutation (K670M/N671L) K670M N671L and the human
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9mutation (K670M/N671L) K670M N671L and the human presenilin 1 (PS1) PS1 carrying the mutation (M146L) M146L under the control of the
11801THY1Thy-1 cell surface antigenThy10.3the mutation (M146L) M146L under the control of the murine Thy1 promoter were generated on the B6D2F1 genetic background in our
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6mice were crossed to generate mice carrying both transgenes (APP/PS1) APP PS1
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9were crossed to generate mice carrying both transgenes (APP/PS1) APP PS1
2527CTSBcathepsin BCATB1.0Second with recombinant mouse cathepsin B (CATB) CATB and cathepsin L (CATL) CATL (both both R_amp_#x26 D Systems
2537CTSL1cathepsin L1CATL1.3recombinant mouse cathepsin B (CATB) CATB and cathepsin L (CATL) CATL (both both R_amp_#x26 D Systems loaded membranes were incubated with
2527CTSBcathepsin BCATB1.0the reaction was followed in the presence of the specific CATB inhibitor CA-074 (1_amp_#xa0;_amp_#x3bc;M, 1_amp_#xa0 _amp_#x3bc M Bachem Weil am Rhein
2527CTSBcathepsin BCATB1.0E-64 (5_amp_#xa0;_amp_#x3bc;M, 5_amp_#xa0 _amp_#x3bc M Sigma in order to inactivate CATB which is also able to hydrolyze the substrate at these
3146ECE1endothelin converting enzyme 1ECE-10.5Cathepsin L cathepsin S as well as ECE-1 activity could be excluded (data data not shown
2527CTSBcathepsin BCATB1.0calculated as the difference between the resulting fluorescence measured with CATB inhibitor and with E-64
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)amyloid1.3The presence of amyloid plaques in APP/PS1 APP PS1 transgenic mice and AD tissues
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6The presence of amyloid plaques in APP/PS1 APP PS1 transgenic mice and AD tissues was confirmed using thioflavine
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9The presence of amyloid plaques in APP/PS1 APP PS1 transgenic mice and AD tissues was confirmed using thioflavine S
6149ITGAMintegrin, alpha M (complement component 3 receptor 3 subunit)CD11b1.0form of CATX the microglia/macrophage microglia macrophage marker rat anti-mouse CD11b (anti-CD11b; anti-CD11b 1 50 alpha chain of a leukocyte-associated protein
4235GFAPglial fibrillary acidic proteinGFAP2.5a large number of cells expressing CATX and the astrocyte-marker GFAP ( Figs 4 B_amp_#x2013 B_amp_#x2033 or the microglial marker CD11b
6149ITGAMintegrin, alpha M (complement component 3 receptor 3 subunit)CD11b1.0GFAP ( Figs 4 B_amp_#x2013 B_amp_#x2033 or the microglial marker CD11b ( Figs 4 C_amp_#x2013 C_amp_#x2033
4235GFAPglial fibrillary acidic proteinGFAP2.5The number of CATX(+) CATX cells expressing GFAP or CD11b was substantially increased in aged mice
6149ITGAMintegrin, alpha M (complement component 3 receptor 3 subunit)CD11b1.0The number of CATX(+) CATX cells expressing GFAP or CD11b was substantially increased in aged mice
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD12.4blot analysis the first changes of CATX immunostaining in the SOD1 transgenics were notable at the age of 3_amp_#xa0 months a
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6APP/PS1 APP PS1 and human AD tissue
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9APP/PS1 APP PS1 and human AD tissue
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6At the age of 9_amp_#xa0 months mice overexpressing both mutant APP and mutant presenilin 1 (APP/PS1) APP PS1 showed numerous thioflavine
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6mice overexpressing both mutant APP and mutant presenilin 1 (APP/PS1) APP PS1 showed numerous thioflavine S-positive plaques in the cerebral cortex
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9overexpressing both mutant APP and mutant presenilin 1 (APP/PS1) APP PS1 showed numerous thioflavine S-positive plaques in the cerebral cortex and
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6In coincidence with the brain of APP/PS1 APP PS1 mice thioflavine S(+) S plaques were surrounded by CATX-loaded
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9In coincidence with the brain of APP/PS1 APP PS1 mice thioflavine S(+) S plaques were surrounded by CATX-loaded cells
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6mouse and (v) v associated with plaques in the APP/PS1 APP PS1 transgenic mouse and human AD cerebral cortex
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9and (v) v associated with plaques in the APP/PS1 APP PS1 transgenic mouse and human AD cerebral cortex
2530CTSEcathepsin ECATE1.3add another enzyme to the group of cathepsins containing CATD CATE and CATB ( Kenessey et al. 1989 Banay-Schwartz et al.
2527CTSBcathepsin BCATB1.0enzyme to the group of cathepsins containing CATD CATE and CATB ( Kenessey et al. 1989 Banay-Schwartz et al. 1992 Nakanishi
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6transgenic mouse model SOD1-G93A and around senile plaques of APP/PS1 APP PS1 transgenics and AD patients
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9mouse model SOD1-G93A and around senile plaques of APP/PS1 APP PS1 transgenics and AD patients
2527CTSBcathepsin BCATB1.0in line with the plaque-associated deposition of other cathepsins like CATB CATD and CATS ( Cataldo and Nixon 1990 Bernstein et
2527CTSBcathepsin BCATB1.0reports showing a strong interaction of several cathepsins such as CATB CATL and CATD with inflammatory factors ( Bever et al.
2537CTSL1cathepsin L1CATL1.3showing a strong interaction of several cathepsins such as CATB CATL and CATD with inflammatory factors ( Bever et al. 1989
2537CTSL1cathepsin L1CATL1.3Schmid et al. 2002 and a role of CATS and CATL in antigen presentation ( Villadangos et al. 1997 Nakagawa et
7762NEUROD1neurogenic differentiation 1beta21.0Via an interaction with beta2 integrins ( Obermajer et al. 2006 it might influence cell
4235GFAPglial fibrillary acidic proteinGFAP2.5with the neuron-marker NeuN (A, A A_amp_#x2032 A_amp_#x2033 the astrocyte-marker GFAP (B, B B_amp_#x2032 B_amp_#x2033 and the microglia-marker CD11b (C, C
6149ITGAMintegrin, alpha M (complement component 3 receptor 3 subunit)CD11b1.0the astrocyte-marker GFAP (B, B B_amp_#x2032 B_amp_#x2033 and the microglia-marker CD11b (C, C C_amp_#x2032 C_amp_#x2033
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6Fig 8._amp_#xa0 CATX expression in APP/PS1 APP PS1 bigenic mice and Alzheimer patients
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9Fig 8._amp_#xa0 CATX expression in APP/PS1 APP PS1 bigenic mice and Alzheimer patients
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6(A_amp_#x2013;D) A_amp_#x2013 D APP/PS1 APP PS1 bigenic animals
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9(A_amp_#x2013;D) A_amp_#x2013 D APP/PS1 APP PS1 bigenic animals
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)amyloid1.3A A_amp_#x2032 Thioflavine and CATX staining of an amyloid plaque in the cerebral cortex of a 9-month-old APP/PS1 APP
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)APP0.6amyloid plaque in the cerebral cortex of a 9-month-old APP/PS1 APP PS1 bigenic animal
9508PSEN1presenilin 1 (Alzheimer disease 3)PS10.9plaque in the cerebral cortex of a 9-month-old APP/PS1 APP PS1 bigenic animal
2536CTSKcathepsin Kcathepsin x1.0in 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.
2536CTSKcathepsin Kcathepsin x1.0these results strongly suggest that cathepsin x is an important player in degenerative processes during normal aging and in pathological conditions.
10417RPS27Aribosomal protein S27aubiquitin1.0all cells are dependent on the two major proteolytic systems within cells the ubiquitin proteasome and the lysosomal system to control the stability function and intracellular localization of a wide variety of proteins rivett 1990 and bohley 1995 .
2536CTSKcathepsin Kcathepsin x1.0cathepsin x catx; synonyms y z p is one of the more recently identified lysosomal cysteine proteases n_amp_#xe4;gler and m_amp_#xe9;nard 1998 .
9508PSEN1presenilin 1 (Alzheimer disease 3)presenilin 11.0transgenic mice expressing the human amyloid precursor protein app with the swedish mutation k670m/n671l and the human presenilin 1 ps1 carrying the mutation m146l under the control of the murine thy1 promoter were generated on the b6d2f1 genetic background in our department.
2527CTSBcathepsin Bcathepsin b1.0second with recombinant mouse cathepsin b catb and cathepsin l catl both r_amp_#x26;d systems loaded membranes were incubated with goat anti mouse catx as primary antibody.
2537CTSL1cathepsin L1cathepsin l1.0second with recombinant mouse cathepsin b catb and cathepsin l catl both r_amp_#x26;d systems loaded membranes were incubated with goat anti mouse catx as primary antibody.
1509CASP8caspase 8, apoptosis-related cysteine peptidasecysteine protease1.0in parallel assays the reaction was followed in the presence of the specific catb inhibitor ca 074 1_amp_#xa0;_amp_#x3bc;m bachem weil am rhein germany and the non specific cysteine protease inhibitor e 64 5_amp_#xa0;_amp_#x3bc;m sigma in order to inactivate catb which is also able to hydrolyze the substrate at these conditions and to evaluate the total cysteine protease activity.
1509CASP8caspase 8, apoptosis-related cysteine peptidasecysteine protease1.0 inhibitor e 64 5_amp_#xa0;_amp_#x3bc;m sigma in order to inactivate catb which is also able to hydrolyze the substrate at these conditions and to evaluate the total cysteine protease activity.
2537CTSL1cathepsin L1cathepsin l1.0cathepsin l cathepsin s as well as ece 1 activity could be excluded data not shown .
2545CTSScathepsin Scathepsin s1.0cathepsin l cathepsin s as well as ece 1 activity could be excluded data not shown .
2527CTSBcathepsin Bcathepsin b1.0the relation of ca 074 to the non inhibited fraction is adequate to cathepsin b activity.
4235GFAPglial fibrillary acidic proteinglial fibrillary acidic protein1.0form proform and mature form of catx the microglia/macrophage marker rat anti mouse cd11b anti cd11b; 1:50; alpha chain of a leukocyte associated protein; serotec the astrocyte marker rabbit anti cow glial fibrillary acidic protein anti gfap; 1:2500; acris and the neuronal marker mouse anti mouse neun 1:700; chemicon hampshire uk .
9508PSEN1presenilin 1 (Alzheimer disease 3)presenilin 11.0at the age of 9_amp_#xa0;months mice overexpressing both mutant app and mutant presenilin 1 app/ps1 showed numerous thioflavine s positive plaques in the cerebral cortex and the hippocampus and this plaque load increased substantially with age data not shown .
2536CTSKcathepsin Kcathepsin x1.0in the present study we characterized the regional and cellular expression as well as the activity of the recently discovered lysosomal cysteine protease cathepsin x in the normal developing and pathological nervous system of the c57bl/6 mouse.
1509CASP8caspase 8, apoptosis-related cysteine peptidasecysteine protease1.0in the present study we characterized the regional and cellular expression as well as the activity of the recently discovered lysosomal cysteine protease cathepsin x in the normal developing and pathological nervous system of the c57bl/6 mouse.
620APPamyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)amyloid beta protein1.0amyloid beta protein precursor|nerve tissue proteins|presenilin 1|sod1 g93a protein|superoxide dismutase|cathepsins|