Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models.
Down syndrome, resulting from trisomy of human chromosome 21, is a common form of chromosomal disorder that results in intellectual disability and altered risk of several medical conditions. Individuals with Down syndrome have a greatly increased risk of Alzheimer's disease (DSAD), due to the p...
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316822 |
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| author | Yixing Wu Karen Cleverley Frances K Wiseman |
| author_facet | Yixing Wu Karen Cleverley Frances K Wiseman |
| author_sort | Yixing Wu |
| collection | DOAJ |
| description | Down syndrome, resulting from trisomy of human chromosome 21, is a common form of chromosomal disorder that results in intellectual disability and altered risk of several medical conditions. Individuals with Down syndrome have a greatly increased risk of Alzheimer's disease (DSAD), due to the presence of the APP gene on chromosome 21 that encodes the amyloid-β precursor protein (APP). APP can be processed to generate amyloid-β, which accumulates in plaques in the brains of people who have Alzheimer's disease and is the upstream trigger of disease. Cathepsin B has potential roles in both APP processing and amyloid-β degradation and has been suggested to contribute to amyloid-β accumulation. An endogenous inhibitor of Cathepsin B, Cystatin B (CSTB), is encoded on chromosome 21. The abundance of this protein is increased in the brains of individuals with DSAD, which may be associated with a decrease in Cathepsin B activity compared to individuals who have Alzheimer's disease in the general population. Whether targeting CSTB can modulate Cathepsin B activity in the context of trisomy of chromosome 21 is unclear. Here we test if reducing CSTB can alter Cathepsin B activity in a mouse and a cellular model of trisomy of chromosome 21. We find that reducing CSTB abundance increases Cathepsin B activity in disomic controls but not in the presence of trisomy of chromosome 21. These findings offer new insights into the role of CSTB in regulating Cathepsin B activity. |
| format | Article |
| id | doaj-art-5ebccf2d809e4c548afccb799e060115 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-5ebccf2d809e4c548afccb799e0601152025-08-20T01:48:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031682210.1371/journal.pone.0316822Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models.Yixing WuKaren CleverleyFrances K WisemanDown syndrome, resulting from trisomy of human chromosome 21, is a common form of chromosomal disorder that results in intellectual disability and altered risk of several medical conditions. Individuals with Down syndrome have a greatly increased risk of Alzheimer's disease (DSAD), due to the presence of the APP gene on chromosome 21 that encodes the amyloid-β precursor protein (APP). APP can be processed to generate amyloid-β, which accumulates in plaques in the brains of people who have Alzheimer's disease and is the upstream trigger of disease. Cathepsin B has potential roles in both APP processing and amyloid-β degradation and has been suggested to contribute to amyloid-β accumulation. An endogenous inhibitor of Cathepsin B, Cystatin B (CSTB), is encoded on chromosome 21. The abundance of this protein is increased in the brains of individuals with DSAD, which may be associated with a decrease in Cathepsin B activity compared to individuals who have Alzheimer's disease in the general population. Whether targeting CSTB can modulate Cathepsin B activity in the context of trisomy of chromosome 21 is unclear. Here we test if reducing CSTB can alter Cathepsin B activity in a mouse and a cellular model of trisomy of chromosome 21. We find that reducing CSTB abundance increases Cathepsin B activity in disomic controls but not in the presence of trisomy of chromosome 21. These findings offer new insights into the role of CSTB in regulating Cathepsin B activity.https://doi.org/10.1371/journal.pone.0316822 |
| spellingShingle | Yixing Wu Karen Cleverley Frances K Wiseman Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models. PLoS ONE |
| title | Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models. |
| title_full | Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models. |
| title_fullStr | Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models. |
| title_full_unstemmed | Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models. |
| title_short | Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse models. |
| title_sort | reduction of cystatin b results in increased cathepsin b activity in disomic but not trisomy 21 human cellular and mouse models |
| url | https://doi.org/10.1371/journal.pone.0316822 |
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