Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis.
OBJECTIVE
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We investigated the expression of MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) in serum and cerebrospinal fluid (CSF) correlating the results with age, disease duration and the clinical course.


METHODS
The material consisted of 30 ALS patients and 15 age-matched healthy controls. ELISA method to determine the expression of MT-MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 in serum and CSF was used. MMP-2 and MMP-9 by zymography was also tested.


RESULTS
In serum MT-MMP-1, MMP-2, MMP-9 and TIMP-1 expression was increased, especially in mild ALS cases. TIMP-2 values were normal. In CSF MT-MMP-1, MMP-2 and TIMP-1 level was either increased or normal, that of MMP-9 was decreased. TIMP-2 did not change. No correlation of MMPs and TIMP-1 expression in serum and CSF and the age of the patients was found. A correlation was observed between MMPs and TIMPs and disease duration.


CONCLUSIONS
Increased level of MMPs and TIMP-1 of ALS patients may reflect the degeneration process of motor neurons and skeletal muscles and/or is associated with tissues remodeling. The low level of MMP-9 in CSF may result from impaired balance between MMP-9 and TIMP-1 and/or its increased intrathecal degradation and physical clearance. Although the role of changed MMPs/TIMPs level in the pathogenesis of ALS is not clear their analysis in serum may be used as prognostic factor and a potential marker for monitoring treatment effects.
Niebroj-Dobosz
I
I
Neuromuscular Unit, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. dobosz@cmdik.pan.pl
Janik
P
P
Sokołowska
B
B
Kwiecinski
H
H
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000134:cerebrospinal fluid; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000134:cerebrospinal fluid; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000134:cerebrospinal fluid; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000134:cerebrospinal fluid; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood / Q000134:cerebrospinal fluid; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood* / Q000134:cerebrospinal fluid*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1