Evidence map›Paper›PMID 30453390›Full record

ArticleGlia2019

PPARβ/δ-agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1ΔE9 astrocytes.

Henna Konttinen, Irina Gureviciene, Minna Oksanen, Alexandra Grubman, Sanna Loppi, Mikko T Huuskonen, Paula Korhonen, Riikka Lampinen, Meike Keuters, Irina Belaya and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Glia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 51 citations in OpenAlex.

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  16. Synthetic PPAR Agonist DTMB Alleviates Alzheimer's Disease Pathology by Inhibition of Chronic Microglial Inflammation in 5xFAD Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 3 countries.

Henna KonttinenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.ORCID 0000-0003-3005-407X
Irina GurevicieneA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Minna OksanenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Alexandra GrubmanDepartment of Anatomy and Developmental Biology, Monash University, Clayton, Australia.
Sanna LoppiA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Mikko T HuuskonenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Paula KorhonenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Riikka LampinenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Meike KeutersA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Irina BelayaA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Heikki TanilaA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Katja M KanninenA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Gundars GoldsteinsA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Gary LandrethStark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana.
Jari KoistinahoA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Tarja MalmA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
University of Eastern Finland · FIFlorey Institute of Neuroscience and Mental Health · AUIndiana University School of MedicineUniversity of Helsinki · FI

Funding

Actions of Nuclear Receptors on TREM2+ myeloid cells and microglia in AD brainRF1AG050597 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI LANDRETH, GARY E. · 2016 to 2016
$2.0M
NIA NIH HHS RF1 AG050597
6 · The paper itself

Abstract

Astrocytes are the gatekeepers of neuronal energy supply. In neurodegenerative diseases, bioenergetics demand increases and becomes reliant upon fatty acid oxidation as a source of energy. Defective fatty acid oxidation and mitochondrial dysfunctions correlate with hippocampal neurodegeneration and memory deficits in Alzheimer's disease (AD), but it is unclear whether energy metabolism can be targeted to prevent or treat the disease. Here we show for the first time an impairment in fatty acid oxidation in human astrocytes derived from induced pluripotent stem cells of AD patients. The impairment was corrected by treatment with a synthetic peroxisome proliferator activated receptor delta (PPARβ/δ) agonist GW0742 which acts to regulate an array of genes governing cellular metabolism. GW0742 enhanced the expression of CPT1a, the gene encoding for a rate-limiting enzyme of fatty acid oxidation. Similarly, treatment of a mouse model of AD, the APP/PS1-mice, with GW0742 increased the expression of Cpt1a and concomitantly reversed memory deficits in a fear conditioning test. Although the GW0742-treated mice did not show altered astrocytic glial fibrillary acidic protein-immunoreactivity or reduction in amyloid beta (Aβ) load, GW0742 treatment increased hippocampal neurogenesis and enhanced neuronal differentiation of neuronal progenitor cells. Furthermore, GW0742 prevented Aβ-induced impairment of long-term potentiation in hippocampal slices. Collectively, these data suggest that PPARβ/δ-agonism alleviates AD related deficits through increasing fatty acid oxidation in astrocytes and improves cognition in a transgenic mouse model of AD.

Indexed as

AdultAnimalsAstrocytesCell DifferentiationCells, CulturedExonsFatty AcidsFemaleHumansInduced Pluripotent Stem CellsMaleMiceMice, Inbred C57BLMice, TransgenicMiddle AgedOxidation-Reduction(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acidFatty AcidsPhenolsPPAR-betaPPAR deltaPresenilin-1PSEN1 protein, humanSulfhydryl CompoundsThiazolesAlzheimer's diseaseastrocytefatty acid oxidationGW0742neurodegenerative diseasesPPARβ/δ

Identifiers

PMID30453390
PMCPMC7526864
OpenAlexW2901611520

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.