Matrix metalloproteinase disorders

Roberts S et al (2000) Matrix metalloproteinases and aggrecanase their role in disorders of the human intervertebral disc. Spine (Phila Pa 1976) 25(23) 3005-3013... 

POEMS is an eponym applied to patients with a variety of plasma cell dyscrasias who present with polyneuropathy, organomegaly, endocrinopathy, an M protein and skin changes this disorder is also referred to as Crow-Fukase syndrome. Additional manifestations of this disorder are pulmonary hypertension, renal failure, a predisposition to thrombosis and congestive heart failure some of these features are likely to be attributable to vascular endothelial growth factor (VEGF) and matrix metalloproteinases, which are often elevated in the plasma of these patients [43]. 

For assessment of degenerative joint disorders as potential side effects of drugs under investigation, a multitude of animal models for osteoarthritis is available, and their respective suitability for the pleiotropic disease aspects have been recently described and discussed by Oegema and Visco (1999), van den Berg (2001), and Brandt (2002). However, novel therapeutic principles, like e.g. the matrix metalloproteinases, have revealed their musculoskeletal side effects as late as in clinical studies only, which then retraced the focus of drug developmental steps back to scrutinize and refine existent models for different applications (Jacobson et al. 1999 Renkiewicz et al. 2003 Peterson 2004). 

Clegg P D, Jones M D, Carter S D 1998 The effect of drugs commonly used in the treatment of equine articular disorders on the activity of equine matrix metalloproteinase-2 and -9. Journal of Veterinary Pharmacology and Therapeutics 21 406-413... 

There is abundant evidence that a diverse array of pro-teinases, particularly those of macrophage or leucocyte origin, have a fundamental role in the injury processes associated with diseases such as ai-antitrypsin deficiency, smoking-related emphysema, cystic fibrosis, bronchiectasis, bronchitis and other respiratory syndromes (Karlinsky and Snider, 1978 Stockley, 1983 Senior and Campbell, 1983 Surer etal., 1984 Janoff, 1985 Snider etal., 1991). However, there has been little exploration of their potential involvement in other airway disorders that have an inflammatory cell aetiology, such as certain types of specialized fibrotic disorders including chronic severe asthma. This is particularly true for the matrix metalloproteinases (MMPs), despite the expectation from their individual substrate specificities (Emonard and... 

Katiyar, S. K. 2006. Matrix metalloproteinase in cancer metastasis Molecular targets for prostate cancer prevention by green tea polyphenols and grape seed proanthocyani-dins. Endocr. Metab. Immune Disord. Drug Target 6 17-24. 

Many enzymes have been associated with carcinogenesis and metastasis. Elevated levels of certain enzymes may be associated with several different diseases or disorders. The two enzymes that we use in our bioactivity screens, matrix metalloproteinase-3 and caspase-1, have been associated with certain cancers and with certain immune disorders. These enzyme assays will be described relative to both applications. 

Nemoto O, Yamagishi M, Yamada H, Kikuchi T, Takaishi H. Matrix metalloproteinase-3 production by human degenerated intervertebral disc. J Spinal Disord 1997 10 493-498. 

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