ArticleNeurochemical research2016
MH84: A Novel γ-Secretase Modulator/PPARγ Agonist--Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer's Disease.
Article in Neurochemical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Simufilam in Alzheimer's Disease: Assessment of Efficacy of a Controversial Drug in Human Neuronal Cell Culture.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro.Antioxidants (Basel, Switzerland) · 2022Article
- The Potential of Gamma Secretase as a Therapeutic Target for Cardiac Diseases.Journal of personalized medicine · 2021Review
- Pioglitazone Reduces Dementia Risk in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Analysis.Journal of clinical medicine · 2018Article
- Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer's Disease.Aging and disease · 2018Review
- MH84 improves mitochondrial dysfunction in a mouse model of early Alzheimer's disease.Alzheimer's research & therapy · 2018Article
- Nutritional and Pharmacological Strategies to Regulate Microglial Polarization in Cognitive Aging and Alzheimer's Disease.Frontiers in aging neuroscience · 2017Review
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Developing new therapeutic strategies for Alzheimer's disease (AD) is a current challenge. Approved drugs merely act symptomatically and delay the progression of the disease for a relatively short period of time. Here, we investigated the effectiveness of MH84 in a cellular HEK293APPwt model of AD, characterized by elevated beta amyloid protein levels (Aβ1-42) and mitochondrial dysfunction. MH84 is a derivate of pirinixic acid belonging to a novel class of γ-secretase modulators, which combines γ-secretase modulation with activation of peroxisome proliferator-activator receptor gamma (PPARγ). The mitochondria modifying Dimebon, the γ-secretase blocker DAPT, and the PPARγ agonist pioglitazone were used as controls. MH84 protects against nitrosative stress, increased mitochondrial respiration, citrate synthase (CS) activity and protein levels of PGC1α indicating enhanced mitochondrial content at nano-molar concentrations. Concurrently, MH84 decreased protein levels of APP, Aβ1-42, and C-terminal fragments at micro-molar concentrations. Both Dimebon and DAPT reduced cellular Aβ1-42 levels. Dimebon improved mitochondrial functions and DAPT decreased mitochondrial membrane potential. Pioglitazone had no effects on APP processing and mitochondrial function. Our data emphasizes MH84 as possible novel therapeutic agent with mitochondria-based mode of action.
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Registered trials
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.