Benussi, L; Ghidoni, R; Steinhoff, T; Alberici, A; Villa, A; Mazzoli, F; Nicosia, F; Barbiero, L; Broglio, L; Feudatari, E; Signorini, S; Finckh, U; Nitsch, R M; Binetti, G (2003). Alzheimer disease-associated cystatin C variant undergoes impaired secretion. Neurobiology of Disease, 13(1):15-21.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine|
|DDC:||610 Medicine & health|
|Deposited On:||08 Sep 2011 08:45|
|Last Modified:||28 Nov 2013 03:15|
|Citations:||Web of Science®. Times cited: 29|
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