IMR Press / FBL / Volume 13 / Issue 9 / DOI: 10.2741/2941

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Involvement of cystatin C in pathophysiology of CNS diseases
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1 Department of Laboratory Medicine, Shimane University Faculty of Medicine, Izumo, Japan
2 Department of Biochemistry and Molecular Medicine, Shimane University Faculty of Medicine, Izumo, Japan
3 Department of Internal Medicine III, Shimane University Faculty of Medicine, Izumo, Japan
4 University Hospital, Shimane University Faculty of Medicine, Izumo, Japan
5 Division of Neurology, UBC Hospital, University of British Columbia, Vancouver, Canada

*Author to whom correspondence should be addressed.


Front. Biosci. (Landmark Ed) 2008, 13(9), 3470–3479;
Published: 1 May 2008

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 β protein (Aβ), and accelerates the amyloidogenicity of Aβ 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 Aβ 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.

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