The amyloidogenic protease inhibitor Cystatin C in health and disease
- Research Opportunity
- PhD, Masters by Research, Honours, Master of Biomedical Science
- Number of Honour Places Available
- Biochemistry and Molecular Biology
- Bio21 Molecular Science and Biotechnology Institute
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Summary Identification of these cells, and characterisation of the mechanisms that control the synthesis and dimerisation of Cst C will lead to the development of therapeutic strategies for the treatment of diseases associated with Cst C.
Cystatin C (Cst C) is a secreted protease inhibitor. Its clinical importance as a regulator of extracellular proteolysis in the vascular system is demonstrated by the association between low serum Cst C levels and formation of atherosclerotic plaques, due in part to uncontrolled proteolytic degradation of arterial elastin. A different property of Cst C that makes this protein clinically relevant is that it can form amyloid fibrils, which are found in the cerebral vasculature of patients with neurodegenerative diseases. Such fibrils are believed to originate by a phenomenon known as “domain swapping”, whereby two Cst C monomers associate by “exchanging” subdomains to generate homodimers. These dimers can then be extended by additional rounds of domain swapping and thus form amyloid fibrils. The cells responsible for Cst C production in vascular disease are unknown. Identification of these cells, and characterisation of the mechanisms that control the synthesis and dimerisation of Cst C will lead to the development of therapeutic strategies for the treatment of diseases associated with Cst C.
Further reading: Xu et al (2014) J Biol Chem 289:9730-9740.
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PhD, Masters by Research, Honours, Master of Biomedical Science
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Research NodeBio21 Molecular Science and Biotechnology Institute
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