کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2034948 | 1072111 | 2008 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A unifying hypothesis for explaining the mechanism of amyloid formation under conditions of increased oxidative stress A unifying hypothesis for explaining the mechanism of amyloid formation under conditions of increased oxidative stress](/preview/png/2034948.png)
Amyloid related organ dysfunction is a common feature of conditions associated with chronic oxidative injury such as diabetes, inflammation, neurodegenerative disorders, renal failure, and natural aging. Matrix metalloproteinases (MMPs) are a family of calcium and zinc-dependent endopeptidases comprised of 23 enzymes in the human. Among these, MMPs 2 and 9 are known as secretable forms, present in all body fluids and susceptible to activation by oxidants. Although MMPs are generally accepted and named for their effect on extracellular matrix turnover, their non-extracellular-matrix targets have emerged recently. Cystatin C (CysC) is a very potent inhibitor of cysteine proteinases, present in all body fluids. Its solubility is determined by its N-terminal sequence. CysC is known to polimerize and form fibrils and has been isolated from amyloids. The CysC isolated from amyloids is in the N-terminal truncated form. My hypothesis regarding amyloid formation is that CysC could be a substrate for MMPs 2 and 9, which upon cleaving the N-terminal off the CysC protein will render it insoluble and promote amyloid formation. Several in vitro studies have demonstrated degradation of CysC by MMPs. The implications of such a degradation in kidney glomerules (where the clearance of CysC occurs) could be of importance for understanding the mechanism of kidney failure e.g. in diabetes. This proposed mechanism for amyloid formation through degradation of CysC by MMPs, can be proposed for all cases of CysC related amyloid formation, such as those seen in cerebrovascular, cardiac and rheumatoid disorders.
Journal: Bioscience Hypotheses - Volume 1, Issue 4, 2008, Pages 209–212