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X Demographics
Mendeley readers
Attention Score in Context
| Title |
MH84 improves mitochondrial dysfunction in a mouse model of early Alzheimer’s disease
|
|---|---|
| Published in |
Alzheimer's Research & Therapy, February 2018
|
| DOI | 10.1186/s13195-018-0342-6 |
| Pubmed ID | |
| Authors |
Maximilian Pohland, Maren Pellowska, Heike Asseburg, Stephanie Hagl, Martina Reutzel, Aljoscha Joppe, Dirk Berressem, Schamim H. Eckert, Mario Wurglics, Manfred Schubert‐Zsilavecz, Gunter P. Eckert |
| Abstract |
Current 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 AβPPSL mice (harboring the Swedish and London mutation in human amyloid precursor protein (APP)) which are characterized by enhanced AβPP processing and cerebral mitochondrial dysfunction, representing a mouse model of early AD. Three-month-old Thy-1 AβPPSL mice received 12 mg/kg b.w. MH84 by oral gavage once a day for 21 days. Mitochondrial respiration was analyzed in isolated brain mitochondria, and mitochondrial membrane potential and ATP levels were determined in dissociated brain cells. Citrate synthase (CS) activity was determined in brain tissues and MitoTracker Green fluorescence was measured in HEK293-AβPPwt and HEK293-AβPPsw cells. Soluble Aβ1-40 and Aβ1-42 levels were determined using ELISA. Western blot analysis and qRT-PCR were used to measure protein and mRNA levels, respectively. MH84 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. MH84 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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 49 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 14% |
| Student > Bachelor | 5 | 10% |
| Student > Doctoral Student | 4 | 8% |
| Researcher | 4 | 8% |
| Professor | 3 | 6% |
| Other | 8 | 16% |
| Unknown | 18 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 20% |
| Medicine and Dentistry | 5 | 10% |
| Neuroscience | 4 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
| Agricultural and Biological Sciences | 3 | 6% |
| Other | 3 | 6% |
| Unknown | 21 | 43% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 February 2018.
All research outputs
#18,587,406
of 23,023,224 outputs
Outputs from Alzheimer's Research & Therapy
#1,177
of 1,243 outputs
Outputs of similar age
#334,984
of 446,078 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#22
of 31 outputs
Altmetric has tracked 23,023,224 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,243 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.9. This one is in the 2nd percentile – i.e., 2% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 446,078 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.