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PPARδ agonist GW0742 ameliorates Aβ1-42-induced hippocampal neurotoxicity in mice.

التفاصيل البيبلوغرافية
العنوان: PPARδ agonist GW0742 ameliorates Aβ1-42-induced hippocampal neurotoxicity in mice.
المؤلفون: An YQ; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Zhang CT; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Du Y; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Zhang M; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Tang SS; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Hu M; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Long Y; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Sun HB; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China., Hong H; Department of Pharmacology, and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China. honghao@cpu.edu.cn.; Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China. honghao@cpu.edu.cn.
المصدر: Metabolic brain disease [Metab Brain Dis] 2016 Jun; Vol. 31 (3), pp. 663-71. Date of Electronic Publication: 2016 Feb 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 8610370 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7365 (Electronic) Linking ISSN: 08857490 NLM ISO Abbreviation: Metab Brain Dis Subsets: MEDLINE
أسماء مطبوعة: Publication: 2005- : Amsterdam : Springer
Original Publication: New York : Plenum, c1986-
مواضيع طبية MeSH: Amyloid beta-Peptides/*toxicity , Hippocampus/*drug effects , Maze Learning/*drug effects , Neuroprotective Agents/*pharmacology , PPAR delta/*agonists , Peptide Fragments/*toxicity , Thiazoles/*pharmacology, Animals ; Apoptosis/drug effects ; Caspase 3/metabolism ; Hippocampus/metabolism ; Interleukin-1beta/metabolism ; Male ; Memory Disorders/drug therapy ; Memory Disorders/metabolism ; Mice ; Mice, Inbred ICR ; NF-kappa B/metabolism ; Neurons/drug effects ; Neurons/metabolism ; PPAR delta/metabolism ; Thiazoles/therapeutic use ; Tumor Necrosis Factor-alpha/metabolism
مستخلص: Amyloid-β deposition is thought to be associated with memory deficits, neuroinflammation, apoptotic responses, and progressive neuronal death manifested in Alzheimer's disease. Peroxisome proliferator-activated receptor δ (PPARδ) is a transcription factor with potent anti-inflammatory effect. In the current study, the effect of GW0742, a selective PPARδ agonist, on Aβ1-42-induced neurotoxicity was investigated in the hippocampus of mice. Intra-hippocampal infusion of aggregated Aβ1-42 oligomer (410pmol/mouse) remarkably damaged learning and memory in the Morris water maze (MWM) and Y-maze tests, accompanied by decreased expression of PPARδ in the hippocampus as confirmed by Western blot. Intra-hippocampal infusion of GW0742 (1.06 mM/mouse) significantly improved Aβ1-42-induced memory deficits in mice, reversed Aβ1-42-induced hippocampal PPARδ down-regulation and repressed Aβ1-42-triggered neuroinflammatory and apoptotic responses, indicated by decreased nuclear NF-κB p65, TNF-α, IL-1β as well as a decrease in cleaved caspase-3 and increased ratio of Bcl-2/Bax in the hippocampus. These results suggest that PPARδ activation ameliorates Aβ1-42-induced hippocampal neurotoxicity, and it might play a crucial role in Alzheimer's disease.
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فهرسة مساهمة: Keywords: Amyloid-β1–42; Memory; Neurotoxicity; Peroxisome proliferator-activated receptor δ
المشرفين على المادة: 0 (Amyloid beta-Peptides)
0 (Interleukin-1beta)
0 (NF-kappa B)
0 (Neuroprotective Agents)
0 (PPAR delta)
0 (Peptide Fragments)
0 (Thiazoles)
0 (Tumor Necrosis Factor-alpha)
0 (amyloid beta-protein (1-42))
4PZK9FJC4Z ((4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid)
EC 3.4.22.- (Caspase 3)
تواريخ الأحداث: Date Created: 20160212 Date Completed: 20180112 Latest Revision: 20220722
رمز التحديث: 20240513
DOI: 10.1007/s11011-016-9800-7
PMID: 26864581
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-7365
DOI:10.1007/s11011-016-9800-7