Premium
Metalloproteinases profile in Creutzfeldt‐Jakob Disease
Author(s) -
Mosnaim Aron David,
Wolf Marion E.,
Cartier Luis A.,
Valenzuela M. Antonieta
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1135-c
Subject(s) - matrix metalloproteinase , zymography , cerebrospinal fluid , gene isoform , disease , pathology , positive correlation , medicine , biology , biochemistry , gene
Our preliminary findings suggest that abnormalities in matrix metalloproteinases (MMPs) activity may be found in the cerebrospinal fluid (CSF) of patients with Creutzfeldt‐Jakob disease (CJD), prompting us to examine the MMP profile in a larger CJD sample. We determined in 16 subjects (12 sporadic and 4 familial CJD), and in 16 age, and sex‐comparable controls the presence of MMP‐2 and MMP‐9 in their active and proenzyme forms, the relative levels of MMP‐3, the effects of four inhibitors of MMPs activity, and the concentration of the CSF 14‐3‐3‐protein, this latter parameter constituting a good diagnostic tool for CJD. Methodology used involved zymography and immunological techniques. Data obtained indicate that CJD patients, in comparison to controls, have a significantly higher positive frequency of pro‐MMP‐9 and of the active form of MMP‐2, along with significantly higher levels of TIMP‐1 and TIMP‐2. We also found a positive correlation between the 14‐3‐3 protein concentration and that of TIMP‐1 and TIMP‐2 levels. Results showing that endogenous MMP cleavage of normal and disease associated isoforms of the human prion give rise to peptides of different sizes, and that the profile of such peptides appear to be characteristic for various CJD subtypes, may allow the molecular classification of such CJD subtypes.