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)

Injection of excitotoxins, such as quinolinic acid (QA), into the striatum has been extensively used as an experimental model of Huntington's disease, while injection of 6-hydroxydopamine (6-OHDA) into the dopaminergic nigrostriatal pathway provides a well established model of Parkinson's disease. In the present study, we have examined the metabolic changes induced by an intrastriatal injection of QA or 6-OHDA using histochemical staining for the metabolic markers cytochrome oxidase (COx) and active glycogene phosphorylase (GPa). Intrastriatal injection of QA produced major changes in COx (decrease of staining) and GPa (increase of staining, except in the core of the lesion where the staining was virtually absent) histochemistry at the level of the striatum and of most of the other basal ganglia nuclei. Although attenuated over time, these changes persisted up to one year after the lesion. On the contrary, after the intrastriatal injection of 6-OHDA (which induces only a partial lesion of the nigrostriatal pathway), we did not observe any remarkable changes in COx or GPa staining. This study illustrates the discrepancies between the morphological changes and metabolic changes that are induced when using these experimental models of neurodegenerative disorders.
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PMID:Metabolic changes after injection of quinolinic acid or 6-hydroxydopamine in the rat striatum: a time-course study using cytochrome oxidase and glycogene phosphorylase a histochemistry. 1087 95

Loss-of-function mutations in the DJ-1/PARK7 gene are responsible for early-onset autosomal-recessive Parkinson's disease. DJ-1 is implicated in the protection of neurons from oxidative stress by scavenging hydrogen peroxide and regulating the transcriptional activity of multiple pathways. Here, we attempted to identify the protein profiles modulated by DJ-1 in MN9D dopaminergic neurons following 6-hydroxydopamine (6-OHDA) treatment. We found that reactive oxygen species (ROS) levels increased in DJ-1-deficient cells that were either untreated or subjected to 6-OHDA treatment. The incidence of apoptosis after 6-OHDA treatment was increased in DJ-1 knockdown cells. Using these cells, we then performed two-dimensional gel electrophoresis in conjunction with mass spectrometry to assess changes in protein profiles before and after 6-OHDA treatment. Several protein spots were positively or negatively altered in DJ-1-deficient cells with or without 6-OHDA. Among the altered proteins, immunoblot analysis confirmed an increase in galectin-7 and a decrease in peroxiredoxin-6 in DJ-1 knockdown cells. Moreover, transcriptional levels of putative p53 target proteins, including selenophosphate synthetase 1 and glycogen phosphorylase, were increased in the DJ-1 knockdown cells. Taken together, our data suggest that increases in pro-apoptotic proteins and decreases in anti-apoptotic proteins render DJ-1 knockdown cells more susceptible to oxidative stress.
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PMID:Proteomic analysis reveals a protective role for DJ-1 during 6-hydroxydopamine-induced cell death. 2254 40