Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 1246 Jun 4

Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS). Increased expression of MMP-9 and TIMPs has been reported in postmortem AD and ALS brain tissue, as well as in ALS cerebrospinal fluid (CSF) and plasma. Although individual studies of MMP and TIMP expression in CSF have included AD and ALS samples, there are no studies comparing the expression of these proteins between neurodegenerative diseases. We measured the levels of matrix metalloproteinases (MMPs)-2 and -9 and the tissue inhibitor of MMPs (e.g. TIMP-1 and TIMP-2) in CSF samples from patients with Parkinson's Disease (PD), Huntington's Disease (HD), AD and ALS as compared to age-matched control patients. There was constitutive expression of the proform of gelatinase A (proMMP-2) on zymography gels in all CSF samples. Unexpectedly, there was an additional gelatinolytic band at 130 kDa of unknown etiology in the CSF samples of patients with PD (61% of patients studied), AD (61%), HD (25%) and ALS (39%). Levels of TIMP-1 were significantly elevated in CSF samples from all disease groups. TIMP-2 was significantly increased in CSF of AD and HD patients. MMP-2 levels did not differ significantly between groups. These findings show that TIMPs are elevated in the CSF of patients with neurodegenerative diseases suggesting a potential role of these endogenous inhibitors of matrix metalloproteinases in neurodegenerative diseases.
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PMID:Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases. 1261 34

Matrix metalloproteinases (MMPs) may play a role in the pathophysiology of Alzheimer's disease (AD). MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) are elevated in postmortem brain tissue of AD patients. MMPs and TIMPs are found in neurons, microglia, vascular endothelial cells and leukocytes. The aim of this study was to determine whether circulating levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 are elevated in the plasma of AD patients. We compared AD patients to age- and gender-matched controls as well as to Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) patients. There was constitutive expression of gelatinase A (MMP-2), and gelatinase B (MMP-9), in all the samples as shown by zymographic analysis. Levels of MMP-9 were significantly (P=0.003) elevated in the plasma of AD patients as compared to controls. Plasma levels of MMP-2, TIMP-1 and TIMP-2 were unchanged. There were no significant changes of MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in PD and ALS samples. TIMP-1 and TIMP-2 were significantly correlated with MMP-9 in the AD patients. ApoE genotyping of plasma samples showed that levels of MMP-2, TIMP-1 and TIMP-2 and MMP-9 were not significantly different between the ApoE subgroups. These findings indicate that circulating levels of MMP-9 are increased in AD and may contribute to disease pathology.
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PMID:Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease. 1268 99

DJ-1 ( PARK7) has been reported to be causative gene of Parkinson disease and also an oncogene. A loss in DJ-1 function can lead to cell death in neurodegenerative disease, or a gain of it can cause unregulated cell survival in cancer, respectively. DJ-1 protein is known to be expressed mainly in trophoblastic cells in the placenta with increased expression in the first trimester compared to later in term. However, its role in trophoblast regulation remains unknown. This study aimed to investigate the effect of DJ-1 regulation on a first trimester extravillous trophoblast cell line, HTR-8/SVneo. The effect of DJ-1 downregulation induced by small-interfering RNA on cell apoptosis, migration, and the pathway to regulate the cell function was assessed. Data of this study showed that DJ-1 downregulation increased apoptosis and reduced migration by regulating matrix metalloproteinase 2 and matrix metalloproteinase 9 in HTR-8/SVneo cells under both ambient and oxidative stress. Changes in cell function were demonstrated to be at least partly dependent on the AKT/S6 kinase beta-1 (S6K1) pathway. In summary, DJ-1 might play a protective role in maintaining trophoblastic cell functions through the AKT/S6K1-based pathway.
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PMID:Effect of DJ-1 Downregulation on the Functions of the First Trimester Extravillous Trophoblasts. 2925 9