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@ARTICLE{Katsouri:136269,
author = {Katsouri, Loukia and Parr, Callum and Bogdanovic, Nenad and
Willem, Michael and Sastre, Magdalena},
title = {{PPAR}γ co-activator-1α ({PGC}-1α) reduces amyloid-β
generation through a {PPAR}γ-dependent mechanism.},
journal = {Journal of Alzheimer's disease},
volume = {25},
number = {1},
issn = {1875-8908},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {DZNE-2020-02591},
pages = {151-162},
year = {2011},
abstract = {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.},
keywords = {Aged / Aged, 80 and over / Alzheimer Disease: metabolism /
Alzheimer Disease: pathology / Amyloid beta-Peptides:
antagonists $\&$ inhibitors / Amyloid beta-Peptides:
biosynthesis / Animals / Cell Line, Tumor / Down-Regulation:
physiology / Female / Heat-Shock Proteins: antagonists $\&$
inhibitors / Heat-Shock Proteins: physiology / Humans / Male
/ Mice / Middle Aged / PPAR gamma: physiology / Peroxisome
Proliferator-Activated Receptor Gamma Coactivator 1-alpha /
Transcription Factors: antagonists $\&$ inhibitors /
Transcription Factors: physiology / Amyloid beta-Peptides
(NLM Chemicals) / Heat-Shock Proteins (NLM Chemicals) / PPAR
gamma (NLM Chemicals) / PPARGC1A protein, human (NLM
Chemicals) / Peroxisome Proliferator-Activated Receptor
Gamma Coactivator 1-alpha (NLM Chemicals) / Transcription
Factors (NLM Chemicals)},
cin = {Ext LMU},
ddc = {610},
cid = {I:(DE-2719)5000048},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:21358044},
doi = {10.3233/JAD-2011-101356},
url = {https://pub.dzne.de/record/136269},
}