ArticleAutophagy2020
Activation of PPARA-mediated autophagy reduces Alzheimer disease-like pathology and cognitive decline in a murine model.
Article in Autophagy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 5 of them syntheses that pooled it.
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.
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.
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Who cites it
209 citing papers in PubMed, 5 syntheses or guidelines pooled it, 369 citations in OpenAlex.
- Efficacy and safety of tACS in older adults with cognitive impairment: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.International journal of molecular sciences · 2023Pooled it
- Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Convergent mitochondrial impairment and apoptosis driven by simultaneous down-regulation of multiple genes at 11p11.2 in Alzheimer's disease.Molecular psychiatry · 2026Article
- Ursolic acid reduces Aβ-driven aggression via Gab1-mediated autophagy and dorsal hippocampal circuit modulation in Alzheimer's disease.Journal of advanced research · 2026Article
- Erjingwan Alleviates Parkinson's Disease via Activation of PPARA-Mediated Autophagy.Applied biochemistry and biotechnology · 2026Article
- IL-6R-CD3-engineered regulatory T cells alleviate neuropathic pain by remodeling the neuroimmune microenvironment.Immunologic research · 2026Article
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Ingenane Diterpenoids fromMolecules (Basel, Switzerland) · 2026Article
- Astrocyte fatty acid metabolism as a driver of risk for major depressive disorder.Nature communications · 2026Article
- Targeting the HDAC4-NHE6-endosomal pH axis restores amyloid-β clearance and cognitive function in Alzheimer's disease mice.Journal of nanobiotechnology · 2026Article
- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Brain Single-Cell Transcriptional Responses to Bexarotene-Activated RXR in an Alzheimer's Disease Model.International journal of molecular sciences · 2026Article
- Single-nucleus RNA sequencing and functional studies of acute methamphetamine-induced cognitive impairment.Communications biology · 2026Article
- Trends and Research Frontiers in Mammalian Target of Rapamycin and Alzheimer's Disease.Molecular neurobiology · 2026Review
- Parthenolide ameliorates bilirubin-induced neuronal cell injury by mediating autophagy.Experimental brain research · 2026Article
- Piezo1-Targeted Magnetoacoustic Nanobubbles Rescue Alzheimer's Pathology by Electromechanical Neuromodulation and Amyloid-β Clearance.ACS nano · 2026Article
- SIR-2.3/SIRT4 loss enhances proteostasis and neuronal resilience via AMPK-induced autophagy in Huntington's disease models.Cell communication and signaling : CCS · 2026Article
149 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer disease (AD) is the most common neurodegenerative disease. An imbalance between the production and clearance of Aβ (amyloid beta) is considered to be actively involved in AD pathogenesis. Macroautophagy/autophagy is a major cellular pathway leading to the removal of aggregated proteins, and upregulation of autophagy represents a plausible therapeutic strategy to combat overproduction of neurotoxic Aβ. PPARA/PPARα (peroxisome proliferator activated receptor alpha) is a transcription factor that regulates genes involved in fatty acid metabolism and activates hepatic autophagy. We hypothesized that PPARA regulates autophagy in the nervous system and PPARA-mediated autophagy affects AD. We found that pharmacological activation of PPARA by the PPARA agonists gemfibrozil and Wy14643 induces autophagy in human microglia (HM) cells and U251 human glioma cells stably expressing the human APP (amyloid beta precursor protein) mutant (APP-p.M671L) and this effect is PPARA-dependent. Administration of PPARA agonists decreases amyloid pathology and reverses memory deficits and anxiety symptoms in APP-PSEN1ΔE9 mice. There is a reduced level of soluble Aβ and insoluble Aβ in hippocampus and cortex tissues from APP-PSEN1ΔE9 mice after treatment with either gemfibrozil or Wy14643, which promoted the recruitment of microglia and astrocytes to the vicinity of Aβ plaques and enhanced autophagosome biogenesis. These results indicated that PPARA is an important factor regulating autophagy in the clearance of Aβ and suggested gemfibrozil be assessed as a possible treatment for AD.
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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.