Cited by 45Alzheimer's disease research and treatmentsProtease and Inhibitor MechanismsCell death mechanisms and regulation

Involvement of cystatin C in pathophysiology of CNS diseases

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Nagai, Atsushi·2008·Frontiers in Bioscience

Abstract

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.

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  1. Barrett, A. J., H. Fritz, A. Grubb, S. Isemura, M. Jarvinen, N. Katunuma, W. Machleidt, W. Muller-Esterl, M. Sasaki & V. Turk: Nomenclature and classification of the proteins homologous with the cysteine-proteinase inhibitor chicken cystatin [letter]. Biochemical Journal, 236, 312 (1986)

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Authors
Nagai, A.
Affiliations
Shimane University (JP)
Corresponding author
Nagai, Atsushi
Venue
Frontiers in Bioscience
Publisher
IMR Press
Published
2008
Volume
Volume
Issue
13
Pages
3470
ISSN
  • 1093-4715 (ISSN-L)
  • 1093-9946
OpenAlex
W1977390583
Cited by
44
References
78
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 4 · 2018: 1 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 3
FWCI
0.22
Type
journal article
Language
en
Open access
Locations
  • Frontiers in bioscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
cystatin C, cerebral amyloid angiopathy, amyloid-beta, Alzheimer's disease, neuronal cell death, apoptosis, cathepsins, cerebrospinal fluid, astrocytes, glial cells, hippocampus, leptomeningeal metastasis, neuroinflammation, amyloid deposition
MeSH terms
Amyloidosis, Central Nervous System Diseases, Cerebrospinal Fluid Proteins, Humans, Inflammation, Genetic Variation, Cystatins, Cerebral Amyloid Angiopathy, Cell Death, Amino Acid Substitution, Cystatin C

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