دورية أكاديمية
أعرض في EDS

A peroxisome proliferator-activated receptor-δ agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.

التفاصيل البيبلوغرافية
العنوان: A peroxisome proliferator-activated receptor-δ agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.
المؤلفون: Martin HL; Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom., Mounsey RB, Sathe K, Mustafa S, Nelson MC, Evans RM, Teismann P
المصدر: Neuroscience [Neuroscience] 2013 Jun 14; Vol. 240, pp. 191-203. Date of Electronic Publication: 2013 Mar 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 7605074 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7544 (Electronic) Linking ISSN: 03064522 NLM ISO Abbreviation: Neuroscience Subsets: MEDLINE
أسماء مطبوعة: Publication: [New York?] : Elsevier Science
Original Publication: Oxford, Elmsford, N. Y., Pergamon Press
مواضيع طبية MeSH: Neuroprotective Agents/*therapeutic use , PPAR delta/*metabolism , Parkinsonian Disorders/*drug therapy , Thiazoles/*therapeutic use, 3,4-Dihydroxyphenylacetic Acid ; Animals ; Cell Count ; Cells, Cultured ; Disease Models, Animal ; Dopamine ; Dose-Response Relationship, Drug ; Female ; Glial Fibrillary Acidic Protein/metabolism ; Humans ; Macrophage-1 Antigen/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; PPAR delta/agonists ; PPAR delta/genetics ; Rats ; Sulfones/pharmacology ; Thiophenes/pharmacology ; Tyrosine 3-Monooxygenase/metabolism
مستخلص: Peroxisome proliferator-activated receptor (PPAR)-γ and PPARα have shown neuroprotective effects in models of Parkinson's disease (PD). The role of the third, more ubiquitous isoform PPARδ has not been fully explored. This study investigated the role of PPARδ in PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model the dopaminergic neurodegeneration of PD. In vitro administration of the PPARδ antagonist GSK0660 (1 μM) increased the detrimental effect of 1-methyl-4-phenylpyridinium iodide (MPP⁺) on cell viability, which was reversed by co-treatment with agonist GW0742 (1 μM). GW0742 alone did not affect MPP⁺ toxicity. PPARδ was expressed in the nucleus of dopaminergic neurons and in astrocytes. Striatal PPARδ levels were increased (over two-fold) immediately after MPTP treatment (30 mg/kg for 5 consecutive days) compared to saline-treated mice. PPARδ heterozygous mice were not protected against MPTP toxicity. Intra-striatal infusion of GW0742 (84 μg/day) reduced the MPTP-induced loss of dopaminergic neurons (5036±195) when compared to vehicle-infused mice (3953±460). These results indicate that agonism of PPARδ provides protection against MPTP toxicity, in agreement with the effects of other PPAR agonists.
(Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; United States HHMI Howard Hughes Medical Institute; R01 HL105278 United States HL NHLBI NIH HHS; R37 DK057978 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (GSK0660)
0 (Glial Fibrillary Acidic Protein)
0 (Macrophage-1 Antigen)
0 (Neuroprotective Agents)
0 (PPAR delta)
0 (Sulfones)
0 (Thiazoles)
0 (Thiophenes)
102-32-9 (3,4-Dihydroxyphenylacetic Acid)
4PZK9FJC4Z ((4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid)
EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
VTD58H1Z2X (Dopamine)
تواريخ الأحداث: Date Created: 20130319 Date Completed: 20131113 Latest Revision: 20230616
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3661980
DOI: 10.1016/j.neuroscience.2013.02.058
PMID: 23500098
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-7544
DOI:10.1016/j.neuroscience.2013.02.058