ArticleScience signaling2021
Activation of PPARα enhances astroglial uptake and degradation of β-amyloid.
Article in Science signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 57 citations in OpenAlex.
- Selective inhibition of TLR2 stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.NeuroImmune pharmacology and therapeutics · 2026Article
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- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Predifferentiation Neurotoxicity of GenX Exposure on hiPSC-Derived Cortical Neurons.Environmental science & technology · 2026Article
- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Amyloid-Frontiers in neuroscience · 2026Review
- Prospect of Muscle-Building Supplement HMB in Alzheimer's Disease.Journal of clinical & experimental immunology · 2026Article
- Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies.Biomedicines · 2025Review
- Phlorizin Ameliorates Amyloid-β Toxicity and Enhances Fatty Acid β-Oxidation inInternational journal of molecular sciences · 2025Article
- Astrocyte Autophagy in Neurodegenerative Diseases: Current Progress in Mechanisms and Therapeutics.Neurochemical research · 2025Review
- Targeting phagocytosis for amyloid-β clearance: implications of morphology remodeling and microglia activation probed by bifunctional chimaeras.Nature communications · 2025Article
- Upregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis.Molecular neurodegeneration · 2025Article
- Cinnamic acid, a natural plant compound, exhibits neuroprotection in a mouse model of Sandhoff disease via PPARα.NeuroImmune pharmacology and therapeutics · 2024Article
- Astrocyte-Neuron Interactions in Alzheimer's Disease.Advances in neurobiology · 2024Review
- Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.Current neuropharmacology · 2024Review
- PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- Identification of Cinnamein, a Component of Balsam of Tolu/Peru, as a New Ligand of PPARα for Plaque Reduction and Memory Protection in a Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease reports · 2024Article
- Article
- Bezafibrate confers neuroprotection in the 5xFAD mouse model of Alzheimer's disease.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- Targeting autophagy in Alzheimer's disease: Animal models and mechanisms.Zoological research · 2023Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Astrocytes are a type of glial cell that are activated in the brain tissue of patients with Alzheimer’s disease to induce the accumulation of amyloid (Aβ). We previously found that a combination of low-dose gemfibrozil (GFB; a drug approved to treat high cholesterol) and retinoic acid (RA; a vitamin A derivative) induces lysosomal bio-genesis through peroxisome proliferator–activated receptor α (PPARα)–mediated transcription of the gene encoding transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy. Here, we found that the same combination (GFB-RA) enhanced the uptake of Aβ from the extracellular space and its subsequent degradation in astrocytes through a PPARα-dependent pathway. GFB-RA stimulated the abundance of both low-density lipoprotein receptor (LDLR) and TFEB in astrocytes through PPARα. LDLR was critical for Aβ uptake, whereas TFEB was critical for its degradation. GFB-RA treatment also increased autophagic flux and lysosomal activity in astrocytes. Consistent with these effects and in a manner dependent on astroglial PPARα, oral administration of GFB-RA switched astroglial activation to a neuroprotective state, lowered Aβ burden in the brain, and improved spatial learning and memory in the 5XFAD mouse model of Alzheimer’s disease. These findings uncover a new function of PPARα in stimulating astroglial uptake and degradation of Aβ and suggest possible repurposing of GFB-RA combination therapy for AD.
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