Elevated levels of matrix metalloproteinases-9 and -1 and of tissue inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy.
We determined the levels and tissue localization of matrix metalloproteinases (MMPs) as well as their endogenous tissue inhibitors (TIMPs) in postmortem brain tissue from 13 patients with progressive supranuclear palsy (PSP) and 8 age-matched controls. MMP-9 expression was significantly increased in both the frontal cortex (p = 0.002) and substantia nigra (p = 0.003) of PSP cases as compared to controls whereas MMP-1 levels were increased in the substantia nigra (p = 0.01) but unchanged in the frontal cortex (p = 0.41). Levels of the endogenous tissue inhibitors of MMPs, TIMP-1 and TIMP-2 were significantly elevated in the substantia nigra (TIMP-1: p = 0.004, TIMP-2: p = 0.01). Levels of TIMPs were unchanged in PSP frontal cortex as compared to control cases. Together, these data show alterations of MMPs and TIMPs in the substantia nigra as well as in the frontal cortex of PSP, consistent with the possibility that alterations in MMPs/TIMPs may contribute to disease pathogenesis.
Lorenzl
Stefan
S
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, Room A-501, New York, NY 10021, USA.
Albers
David S
DS
Chirichigno
Jason W
JW
Augood
Sarah J
SJ
Beal
M Flint
MF
D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western / Q000379:methods; D001923:Brain Chemistry; D016022:Case-Control Studies; D004587:Electrophoresis, Agar Gel / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011180:Postmortem Changes; D013378:Substantia Nigra / Q000201:enzymology*; D013494:Supranuclear Palsy, Progressive / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1