期刊
NEUROBIOLOGY OF AGING
卷 25, 期 8, 页码 1033-1043出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2003.11.006
关键词
Alzheimer's disease; cerebral amyloid angiopathy; cystatin C; protease inhibitor; amyloid beta; beta amyloid precursor protein
资金
- NIA NIH HHS [AG13705, AG08721, AG17617] Funding Source: Medline
- NINDS NIH HHS [NS42029] Funding Source: Medline
The colocalization of cystatin C, an inhibitor of cysteine proteases, with amyloid beta (Abeta) in parenchymal and vascular amyloid deposits in brains of Alzheimer's disease (AD) patients may reflect cystatin C involvement in annyloidogenesis. We therefore sought to determine the association of cystatin C with Abeta. Immunofluorescence analysis of transfected cultured cells demonstrated colocalization of cystatin C and beta amyloid precursor protein (betaAPP) intracellularly and on the cell surface. Western blot analysis of immunoprecipitated cell lysate or medium proteins revealed binding of cystatin C to full-length betaAPP and to secreted betaAPP (sbetaAPP). Deletion mutants of betaAPP localized the cystatin C binding site within betaAPP to the Abeta region. Cystatin C association with betaAPP resulted in increased sbetaAPP but did not affect levels of secreted Abeta. Analysis of the association of cystatin C and Abeta demonstrated a specific, saturable and high affinity binding between cystatin C and both Abeta(1-42) and Abeta(1-40). Notably, cystatin C association with All results in a concentration-dependent inhibition of Abeta fibril formation. (C) 2003 Elsevier Inc. All rights reserved.
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