Expression of MMP-2, MMP-9, and MMP-1 and their endogenous counterregulators TIMP-1 and TIMP-2 in postmortem brain tissue of Parkinson's disease

Abstract

We investigated the levels and tissue localization of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in postmortem brain tissue from Parkinson's disease (PD) and age-matched control cases. Using zymography, we found reduced MMP-2 levels in PD cases in the substantia nigra as compared to controls; levels of MMP-2 were not significantly changed in the cortex and the hippocampus. MMP-9 levels were unchanged in the investigated brain regions. Immunohistochemically, MMP-2 was localized primarily in astrocytes and microglia cells, whereas MMP-9 was predominantly neuronal. Levels of TIMP-1, an endogenous tissue inhibitor of MMPs, were significantly elevated in the substantia nigra, but not in the cortex and hippocampus. TIMP-2 levels were unchanged in PD. To investigate whether increased TIMP-1 levels in the substantia nigra might be due to increased MMP-1 expression, we measured MMP-1 levels using Western blots. MMP-1 levels were unchanged in PD cases compared to controls. Together, these data show alterations of MMP-2 and TIMP-1 in the substantia nigra of PD, consistent with the possibility that alterations in MMPs/TIMPs may contribute to disease pathogenesis.