Document Detail


Involvement of cystatin C in pathophysiology of CNS diseases.
MedLine Citation:
PMID:  18508448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cystatin C Leu68Gln variant is known to induce amyloid deposition in cerebral arterioles, resulting in Icelandic type cerebral amyloid angiopathy (CAA). Wild-type cystatin C is also observed in solitary CAA involving amyloid beta protein (Abeta), and accelerates the amyloidogenicity of Abeta in vitro. In neurological inflammatory diseases and leptomeningeal metastasis, low cystatin C levels are accompanied with high activities of cathepsins in the cerebrospinal fluid. Among the cells in CNS, astrocytes appear to secrete cystatin C in response to various proteases and cytokines. Co-localization of Abeta and cystatin C in the brains of Alzheimer's disease (AD) led to the hypothesis that cystatin C is involved in the disease process. We demonstrated that cystatin C microinjection into rat hippocampus induced neuronal cell death in dentate gyrus. Furthermore, apoptotic cell death was observed in neuronal cells treated with cystatin C in vitro. Up-regulation of cystatin C was observed in glial cells with neuronal cell death in vivo. These findings indicate the involvement of cystatin C in the process of neuronal cell death.
Authors:
Atsushi Nagai; Masaharu Terashima; Abdullah Md Sheikh; Yoshitomo Notsu; Koichi Shimode; Shuhei Yamaguchi; Shotai Kobayashi; Seung U Kim; Junichi Masuda
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Publication Detail:
Type:  Journal Article; Review     Date:  2008-05-01
Journal Detail:
Title:  Frontiers in bioscience : a journal and virtual library     Volume:  13     ISSN:  1093-4715     ISO Abbreviation:  Front. Biosci.     Publication Date:  2008  
Date Detail:
Created Date:  2008-05-29     Completed Date:  2008-09-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9709506     Medline TA:  Front Biosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3470-9     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine, Shimane University Faculty of Medicine, Izumo, Japan. anagai@med.shimane-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Amyloidosis / genetics,  pathology
Cell Death
Central Nervous System Diseases / pathology,  physiopathology*
Cerebral Amyloid Angiopathy / genetics,  pathology
Cerebrospinal Fluid Proteins / physiology
Cystatin C
Cystatins / cerebrospinal fluid,  genetics,  physiology*
Genetic Variation
Humans
Inflammation / prevention & control
Chemical
Reg. No./Substance:
0/CST3 protein, human; 0/Cerebrospinal Fluid Proteins; 0/Cst3 protein, rat; 0/Cystatin C; 0/Cystatins

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