title: Metalloproteinase ADAMTS-1 but not ADAMTS-5 is manifold overexpressed in neurodegenerative disorders as Down syndrome, Alzheimer's and Pick's disease.
abstract: ADAMTS-1 is a disintegrin and metalloproteinase with thrombospondin 1 (TSP1)-like motifs with ubiquitous though variable expression. Natural substrates of this protease are proteoglycans as aggrecan and versican and null mutant mice propose a role for growth, fertility, organ structure and function. As the gene for this protein is encoded on chromosome 21 and maybe overexpressed due to the gene dosage hypothesis based upon the presence of a third chromosome in trisomy 21, we decided to study expression in Down syndrome (DS) brain and used brains of patients with Alzheimer's (AD) and Pick's disease (PD) as controls. Frontal cortex of controls, DS, AD and PD were homogenized and extracted proteins were used for immunoblotting using antibodies against ADAMTS-1 and ADAMTS-5. ADAMTS-1-immunoreactivity was manifold increased in brain with DS and neurodegeneration, whereas ADAMTS-5 levels were comparable. Overexpression of this metalloproteinase maybe specifically involved in proteoglycan degradation and handling in brain of patients with neurodegenerative disease which in turn may lead to or reflect pathological lesions in DS, AD and PD brain. The manifold overexpression of ADAMTS-1 may be used as marker protein for neurodegeneration.
authors.affiliation: CChem, FRSC (UK), Medical University of Vienna, Department of Pediatrics, Währinger Gürtel 18, A 1090 Vienna, Austria.
authors.forename: Rosa Ferrando
authors.initials: RF
authors.lastname: Miguel
authors.forename: Arnold
authors.initials: A
authors.lastname: Pollak
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000071116:ADAMTS5 Protein; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology*; D015153:Blotting, Western / Q000379:methods; D019483:Disintegrins / Q000378:metabolism*; D004314:Down Syndrome / Q000201:enzymology*; D005625:Frontal Lobe / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D020774:Pick Disease of the Brain / Q000201:enzymology*; D011180:Postmortem Changes
chemical_list: D019483:Disintegrins; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D008666:Metalloendopeptidases