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001     136269
005     20240321220035.0
024 7 _ |a 10.3233/JAD-2011-101356
|2 doi
024 7 _ |a pmid:21358044
|2 pmid
024 7 _ |a 1387-2877
|2 ISSN
024 7 _ |a 1875-8908
|2 ISSN
024 7 _ |a altmetric:49675411
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037 _ _ |a DZNE-2020-02591
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Katsouri, Loukia
|b 0
245 _ _ |a PPARγ co-activator-1α (PGC-1α) reduces amyloid-β generation through a PPARγ-dependent mechanism.
260 _ _ |a Amsterdam
|c 2011
|b IOS Press
264 _ 1 |3 print
|2 Crossref
|b IOS Press
|c 2011-06-14
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a We have previously reported that the nuclear receptor peroxisome proliferator activated receptor-γ (PPARγ) regulates the transcription of β-secretase (BACE1), a key enzyme involved in amyloid-β (Aβ) generation. Here, we aimed to investigate the role of PPARγ coactivator-1α (PGC-1α), which controls major metabolic functions through the co-activation of PPARγ and other transcription factors. Western blotting experiments with nuclear extracts from brain cortex of AD cases and controls showed a reduction in the levels of PGC-1α in AD patients. PGC-1α overexpression in N2a neuroblastoma cells induced a decrease in the levels of secreted Aβ and an increase in the levels of non-amyloidogenic soluble AβPPα. The decrease in Aβ after exogenous expression of PGC-1α was a consequence of reduced BACE1 expression and transcription, together with a decrease in BACE1 promoter activity. In addition, we detected a significant reduction in β-secretase activity by measuring the levels of β-carboxy terminus fragment (β-CTFs) and by using a commercial assay for β-secretase. In contrast, down-regulation of PGC-1α levels by transfection with PGC-1α siRNA increased BACE1 expression. These effects appeared to be dependent on PPARγ, because PGC-1α did not affect Aβ and BACE1 levels in N2a cells transfected with PPARγ siRNA or in PPARγ knockout fibroblasts. In conclusion, since PGC-1α appears to decrease Aβ generation, therapeutic modulation of PGC-1α could have real potential as a treatment for AD.
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588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a Heat-Shock Proteins
|2 NLM Chemicals
650 _ 7 |a PPAR gamma
|2 NLM Chemicals
650 _ 7 |a PPARGC1A protein, human
|2 NLM Chemicals
650 _ 7 |a Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
|2 NLM Chemicals
650 _ 7 |a Transcription Factors
|2 NLM Chemicals
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: biosynthesis
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Down-Regulation: physiology
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Heat-Shock Proteins: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Heat-Shock Proteins: physiology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a PPAR gamma: physiology
|2 MeSH
650 _ 2 |a Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
|2 MeSH
650 _ 2 |a Transcription Factors: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Transcription Factors: physiology
|2 MeSH
700 1 _ |a Parr, Callum
|b 1
700 1 _ |a Bogdanovic, Nenad
|b 2
700 1 _ |a Willem, Michael
|0 P:(DE-2719)9000433
|b 3
|u dzne
700 1 _ |a Sastre, Magdalena
|0 P:(DE-HGF)0
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|e Corresponding author
773 1 8 |a 10.3233/jad-2011-101356
|b : IOS Press, 2011-06-14
|n 1
|p 151-162
|3 journal-article
|2 Crossref
|t Journal of Alzheimer's Disease
|v 25
|y 2011
|x 1875-8908
773 _ _ |a 10.3233/JAD-2011-101356
|g Vol. 25, no. 1, p. 151 - 162
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|n 1
|q 25:1<151 - 162
|p 151-162
|t Journal of Alzheimer's disease
|v 25
|y 2011
|x 1875-8908
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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