Alzheimer disease-associated cystatin C variant undergoes impaired secretion
CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2003-06-01
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| Series: | Neurobiology of Disease |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996103000123 |
| _version_ | 1818673408342228992 |
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| author | Luisa Benussi Roberta Ghidoni Tiana Steinhoff Antonella Alberici Aldo Villa Federica Mazzoli Francesca Nicosia Laura Barbiero Laura Broglio Enrica Feudatari Simona Signorini Ulrich Finckh Roger M. Nitsch Giuliano Binetti |
| author_facet | Luisa Benussi Roberta Ghidoni Tiana Steinhoff Antonella Alberici Aldo Villa Federica Mazzoli Francesca Nicosia Laura Barbiero Laura Broglio Enrica Feudatari Simona Signorini Ulrich Finckh Roger M. Nitsch Giuliano Binetti |
| author_sort | Luisa Benussi |
| collection | DOAJ |
| description | CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease. |
| first_indexed | 2024-12-17T07:55:19Z |
| format | Article |
| id | doaj.art-30bfaa7317784c41b8c32651ef645024 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T07:55:19Z |
| publishDate | 2003-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-30bfaa7317784c41b8c32651ef6450242022-12-21T21:57:44ZengElsevierNeurobiology of Disease1095-953X2003-06-011311521Alzheimer disease-associated cystatin C variant undergoes impaired secretionLuisa Benussi0Roberta Ghidoni1Tiana Steinhoff2Antonella Alberici3Aldo Villa4Federica Mazzoli5Francesca Nicosia6Laura Barbiero7Laura Broglio8Enrica Feudatari9Simona Signorini10Ulrich Finckh11Roger M. Nitsch12Giuliano Binetti13Neurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyNeurobiology Lab, IRCCS Centro San Giovanni di Dio, Italy; Department of Psychiatry Research, University of Zurich, Switzerland; Department of Human Genetics, University Hospital, Hamburg-Eppendorf, GermanyCST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease.http://www.sciencedirect.com/science/article/pii/S0969996103000123 |
| spellingShingle | Luisa Benussi Roberta Ghidoni Tiana Steinhoff Antonella Alberici Aldo Villa Federica Mazzoli Francesca Nicosia Laura Barbiero Laura Broglio Enrica Feudatari Simona Signorini Ulrich Finckh Roger M. Nitsch Giuliano Binetti Alzheimer disease-associated cystatin C variant undergoes impaired secretion Neurobiology of Disease |
| title | Alzheimer disease-associated cystatin C variant undergoes impaired secretion |
| title_full | Alzheimer disease-associated cystatin C variant undergoes impaired secretion |
| title_fullStr | Alzheimer disease-associated cystatin C variant undergoes impaired secretion |
| title_full_unstemmed | Alzheimer disease-associated cystatin C variant undergoes impaired secretion |
| title_short | Alzheimer disease-associated cystatin C variant undergoes impaired secretion |
| title_sort | alzheimer disease associated cystatin c variant undergoes impaired secretion |
| url | http://www.sciencedirect.com/science/article/pii/S0969996103000123 |
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