Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal processing and aggregation of synaptic proteins might play an important role in the pathogenesis of neurodegenerative disorders. Among them, amyloid precursor protein (APP) has been clearly associated with Alzheimer's disease (AD) and various transgenic (tg) animal models have been developed where mutant APP is overexpressed under the regulatory control of neuronal promoters. These studies have shown that AD-like pathology (namely plaques and synapse damage) begins to develop at 6-8 months of age in mice expressing human APP under Thy1, platelet-derived growth factor (B-chain) or protease-resistant prion protein promoters, provided that levels of APP are higher than 5-7 fold of endogenous levels. None of these models have shown the presence of tangles; however, tau-immunoreactive neurites in plaques and astroglial/microglial activation are observed after 12 months of age. Neuronal loss and alterations of synaptic function and connectivity are found in the CA1 region in the PDAPP tg mice lacking the Swiss Webster background. Co-expression of other genes associated with AD modify this phenotype, for example, mutant presenilin 1 accelerates the onset of plaque formation, transforming growth factor beta enhances vascular amyloidosis, and apolipoprotein E decreases amyloid deposition. In conclusion, tg mice which are capable of mimicking some aspects of AD (provided that high enough levels of expression are achieved) can potentially be used to test novel drugs for the treatment of neurodegenerative disorders.
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PMID:Genetically altered transgenic models of Alzheimer's disease. 1096 30

Adipose tissue contains a mesenchymal stem cell (MSC) population known as adipose-derived stem cells (ASCs) capable of differentiating into different cell types. Our aim was to induce hepatic transdifferentiation of ASCs by sequential exposure to several combinations of cytokines, growth factors, and hormones. The most efficient hepatogenic protocol includes fibroblastic growth factors (FGF) 2 and 4 and epidermal growth factor (EGF) (step 1), hepatocyte growth factor (HGF), FGF2, FGF4, and nicotinamide (Nic) (step 2), and oncostatin M (OSM), dexamethasone (Dex), and insulin-tranferrin-selenium (step 3). This protocol activated transcription factors [GATA6, Hex, CCAAT/enhancer binding protein alpha and beta (CEBPalpha and beta), peroxisome proliferator-activated receptor-gamma, coactivator 1 alpha (PGC1alpha), and hepatocyte nuclear factor 4 alpha (HNF4alpha)], which promoted a characteristic hepatic phenotype, as assessed by new informative markers for the step-by-step hepatic transdifferentiation of hMSC [early markers: albumin (ALB), alpha-2-macroglobuline (alpha2M), complement protein C3 (C3), and selenoprotein P1 (SEPP1); late markers: cytochrome P450 3A4 (CYP3A4), apolipoprotein E (APOE), acyl-CoA synthetase long-chain family member 1 (ACSL1), and angiotensin II receptor, type 1 (AGTR1)]. The loss of adipose adult stem cell phenotype was detected by losing expression of Thy1 and inhibitor of DNA binding 3 (Id3). The reexpression of phosphoenolpyruvate corboxykinase (PEPCK), apolipoprotein C3 (APOCIII), aldolase B (ALDOB), and cytochrome P450 1A2 (CYP1A2) was achieved by transduction with a recombinant adenovirus for HNF4alpha and finally hepatic functionality was also assessed by analyzing specific biochemical markers. We conclude that ASCs could represent an alternative tool in clinical therapy for liver dysfunction and regenerative medicine.
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PMID:Sequential hepatogenic transdifferentiation of adipose tissue-derived stem cells: relevance of different extracellular signaling molecules, transcription factors involved, and expression of new key marker genes. 1966 Jan 80