Evidence map›Paper›PMID 29433569›Full record

ArticleAlzheimer's research & therapy2018

MH84 improves mitochondrial dysfunction in a mouse model of early Alzheimer's disease.

Maximilian Pohland, Maren Pellowska, Heike Asseburg, Stephanie Hagl, Martina Reutzel, Aljoscha Joppe, Dirk Berressem, Schamim H Eckert, Mario Wurglics, Manfred Schubert-Zsilavecz and 1 more

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

Article in Alzheimer's research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-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

18 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Pelargonidin-Antioxidants (Basel, Switzerland) · 2022
    Article
  13. Article
  14. Extracellular Mitochondria Signals in CNS Disorders.Frontiers in cell and developmental biology · 2021
    Review
  15. Review
  16. Review
  17. Article
  18. Review
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

11 authors at 2 institutions in 1 country.

Maximilian PohlandInstitute of Pharmacology, Goethe University, Frankfurt, Germany.
Maren PellowskaInstitute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany.
Heike AsseburgInstitute of Pharmacology, Goethe University, Frankfurt, Germany.
Stephanie HaglInstitute of Pharmacology, Goethe University, Frankfurt, Germany.
Martina ReutzelInstitute of Nutritional Sciences, Justus-Liebig-University, Giessen, Germany.
Aljoscha JoppeInstitute of Pharmacology, Goethe University, Frankfurt, Germany.
Dirk BerressemInstitute of Pharmacology, Goethe University, Frankfurt, Germany.
Schamim H EckertInstitute of Pharmacology, Goethe University, Frankfurt, Germany.
Mario WurglicsInstitute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany.
Manfred Schubert-ZsilaveczInstitute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany.
Gunter P EckertInstitute of Nutritional Sciences, Justus-Liebig-University, Giessen, Germany. gunter.eckert@ernaehrung.uni-giessen.de.
Goethe University Frankfurt · DEUniversity of Giessen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCurrent approved drugs for Alzheimer's disease (AD) only attenuate symptoms, but do not cure the disease. The pirinixic acid derivate MH84 has been characterized as a dual gamma-secretase/proliferator activated receptor gamma (PPARγ) modulator in vitro. Pharmacokinetic studies in mice showed that MH84 is bioavailable after oral administration and reaches the brain. We recently demonstrated that MH84 improved mitochondrial dysfunction in a cellular model of AD. In the present study, we extended the pharmacological characterization of MH84 to 3-month-old Thy-1 AβPP

methodsThree-month-old Thy-1 AβPP

resultsMH84 reduced cerebral levels of the β-secretase-related C99 peptide and of Aβ40 levels. Mitochondrial dysfunction was ameliorated by restoring complex IV (cytochrome-c oxidase) respiration, mitochondrial membrane potential, and levels of ATP. Induction of PPARγ coactivator-1α (PGC-1α) mRNA and protein expression was identified as a possible mode of action that leads to increased mitochondrial mass as indicated by enhanced CS activity, OXPHOS levels, and MitoTracker Green fluorescence.

conclusionsMH84 modulates β-secretase processing of APP and improves mitochondrial dysfunction by a PGC-1α-dependent mechanism. Thus, MH84 seems to be a new promising therapeutic agent with approved in-vivo activity for the treatment of AD.

Indexed as

Adenosine TriphosphateAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainBrain-Derived Neurotrophic FactorCaproatesDisease Models, AnimalElectron Transport Complex IVHEK293 CellsHumansMembrane Potential, MitochondrialMice, Inbred C57BLMice, TransgenicMitochondriaAdenosine TriphosphateAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Amyloid beta-Protein PrecursorAPP protein, humanBdnf protein, mouseBrain-Derived Neurotrophic FactorCaproatesElectron Transport Complex IVgamma-secratase modulator MH84Neuroprotective AgentsPeptide FragmentsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mousePyrimidinesRNA, MessengerAlzheimer’s diseaseAmyloid-betaAPP processingMitochondrial dysfunctionPGC-1 alphaPPAR gamma activator

Identifiers

PMID29433569
PMCPMC5809956
OpenAlexW2807658485

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.