2002
DOI: 10.1046/j.1471-4159.2002.00990.x
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Protective action of the peroxisome proliferator‐activated receptor‐γ agonist pioglitazone in a mouse model of Parkinson's disease

Abstract: We examined the effect of pioglitazone, a peroxisome proliferator-activated receptor-c (PPARc) agonist of the thiazolidinedione class, on dopaminergic nerve cell death and glial activation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. The acute intoxication of C57BL/6 mice with MPTP led to nigrostriatal injury, as determined by tyrosine hydroxylase (TH) immunocytochemistry, and HPLC detection of striatal dopamine and metabolites. Damage to the nigrostriatal dopa… Show more

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Cited by 365 publications
(257 citation statements)
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“…This scenario would be akin to a 'preconditioning' effect in which a drug is beneficial by mildly impairing mitochondrial respiration. In support of these ideas, pioglitazone has been shown to be protective in situations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration in the mouse model of Parkinson's disease [7] and in acute metabolic stress caused by ischaemia [41]. Extrapolating these findings to diabetic patients should nevertheless be done with caution.…”
Section: Discussionmentioning
confidence: 92%
See 1 more Smart Citation
“…This scenario would be akin to a 'preconditioning' effect in which a drug is beneficial by mildly impairing mitochondrial respiration. In support of these ideas, pioglitazone has been shown to be protective in situations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration in the mouse model of Parkinson's disease [7] and in acute metabolic stress caused by ischaemia [41]. Extrapolating these findings to diabetic patients should nevertheless be done with caution.…”
Section: Discussionmentioning
confidence: 92%
“…The finding that thiazolidinediones are potent inhibitors of inflammation [3][4][5] has prompted several clinical trials testing the effects of thiazolidinediones in neurological diseases such as Alzheimer's disease and multiple sclerosis, in which inflammation contributes to pathogenesis [6]. The antiinflammatory properties of pioglitazone in the brain have also been shown in murine models of acute [7] and chronic [8] inflammation, when this thiazolidinedione was administered to the animals orally. Both the metabolic and inflammatory actions of thiazolidinediones have been attributed to changes in gene expression mediated by peroxisome proliferator-activated nuclear receptor (PPAR)-γ, of which thiazolidinediones are ligands [3].…”
Section: Introductionmentioning
confidence: 99%
“…Their efficacy in improving insulin sensitivity correlates with the reduction of diabetes-induced acute brain damage, since chronic hyperglycemia is a major risk factor for neuropathy and vasculopathy (81). Treatment with TZDs significantly reduced the symptoms associated with Parkinson's disease and showed improved protection of dopaminergic neurons (21).…”
Section: Ppar-gamma Effects In the Cnsmentioning
confidence: 99%
“…The activation of one of their three major subtypesFPPARgFcontributes by reducing the secretion of proinflammatory cytokines and neurotoxic substances in brain cells (Petrova et al, 1999), that is downregulating inducible nitric-oxide synthase expression, reducing cell death in in vitro (Heneka et al, 1999) and in vivo (Heneka et al, 2000) brain experiments. The possible clinical use of PPARg agonists in neurological diseases has been demonstrated in experimental models, and this has led to the possibility that PPARg agonists provide protection in neurodegenerative diseases, such as Alzheimer's disease (Heneka et al, 2001), stroke (Uryu et al, 2002), Parkinson's disease (Breidert et al, 2002), and multiple sclerosis (Niino et al, 2001).…”
Section: Introductionmentioning
confidence: 99%