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

Irregularities in motor response after continuing levodopa therapy of Parkinson disease (the "on-off effect") were assessed with the addition of L-alpha-methyldopa hydrazine (carbidopa) in a double-blind study. Thirteen of 20 patients improved while receiving carbidopa and levodopa while only four of 17 patients improved while receiving placebo and levodopa. Twenty-three of 37 patients improved in a subsequent non-blind trial of carbidopa plus levodopa. Improvement was not dependent on an increase in dose or frequency of levodopa administration. Adverse effects included dyskinesia, imbalance, and confusion; nausea was eliminated. On patient died of glomerulonephritis that predated the drug trial, but worsened progressively during and after it. Carbidopa's suppression of the "on-off effect" suggests that extracerbral factors may be important in this phenomenon.
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PMID:Treatment of "on-off effect" with a dopa decarboxylase inhibitor. 115 14

The complement system is a critical component of innate immunity that requires regulation to avoid inappropriate activation. This regulation is provided by many proteins, including complement factor H (CFH), a critical regulator of the alternative pathway of complement activation. Given its regulatory function, mutations in CFH have been implicated in diseases such as age-related macular degeneration and membranoproliferative glomerulonephritis, and central nervous system diseases such as Alzheimer's disease, Parkinson's disease, and a demyelinating murine model, experimental autoimmune encephalomyelitis (EAE). There have been few investigations on the transcriptional regulation of CFH in the brain and CNS. Our studies show that CFH mRNA is present in several CNS cell types. The murine CFH (mCFH) promoter was cloned and examined through truncation constructs and we show that specific regions throughout the promoter contain enhancers and repressors that are positively regulated by inflammatory cytokines in astrocytes. Database mining of these regions indicated transcription factor binding sites conserved between different species, which led to the investigation of specific transcription factor binding interactions in a 241 base pair (bp) region at -416 bp to -175 bp that showed the strongest activity. Through supershift analysis, it was determined that c-Jun and c-Fos interact with the CFH promoter in astrocytes in this region. These results suggest a relationship between cell cycle and complement regulation, and how these transcription factors and CFH affect disease will be a valuable area of investigation.
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PMID:c-Jun and c-Fos regulate the complement factor H promoter in murine astrocytes. 2192 Jun 6

Receptor-activity modifying proteins (RAMPs) belong to a single family of transmembrane proteins. RAMPs determine ligand specificity of G-protein coupled receptors; calcitonin receptor and the calcitonin-receptor like receptor (CLR). To date, three members of RAMP family (RAMP-1, -2, -3) have been identified. The co-expression of RAMP-1 with CLR constitutes the calcitonin gene related peptide receptor whereas the association of the RAMP-2 or RAMP-3 with CLR forms the adrenomedullin (AM) receptor. Alterations in signaling and subcellular distribution of G-protein coupled receptors can be responsible for the regulation of many disease conditions. These changes may be mediated by the different isoforms of RAMPs associated with such receptors. In this chapter, we describe the differential responses associated with upregulation of RAMPs in disease conditions. For instance, the upregulation of all three RAMP isoforms contributes to the cardioprotective effects of the CLR/RAMP ligands. On the other hand, strong evidence exists for the involvement of AM in various cancers and that its action is mediated by the upregulation of RAMP isoforms, RAMP-2 and -3. Though limited, a few studies have been reported on the differential response associated with the upregulation of RAMP in other disease conditions such as sepsis, liver cirrhosis, glomerulonephritis, Type 1 diabetes and Parkinson's disease. Thus, the regulation of RAMP expression is involved in the pathophysiology associated with various diseases.
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PMID:Regulation of RAMP expression in diseases. 2243 10