ArticleMolecular neurodegeneration2023
Oleoylethanolamide facilitates PPARα and TFEB signaling and attenuates Aβ pathology in a mouse model of Alzheimer's disease.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- Targeting microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and therapeutic approaches.Frontiers in immunology · 2026Review
- Capsaicin Alleviates Autophagy-Lysosomal Dysfunction via PPARA-Mediated V-ATPase Subunit ATP6V0E1 Signaling in 3xTg-AD Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Phlorizin Ameliorates Amyloid-β Toxicity and Enhances Fatty Acid β-Oxidation inInternational journal of molecular sciences · 2025Article
- Potential of phytochemicals in the treatment of Alzheimer disease by modulating lysosomal dysfunction: a systematic review.Chinese medicine · 2025Review
- Review
- From Obesity to Mitochondrial Dysfunction in Peripheral Tissues and in the Central Nervous System.Biomolecules · 2025Review
- Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances.Signal transduction and targeted therapy · 2025Review
- Regulatory Mechanisms and Therapeutic Implications of Lysosomal Dysfunction in Alzheimer's Disease.International journal of biological sciences · 2025Review
- Region-Specific Gene Expression Changes Associated with Oleoylethanolamide-Induced Attenuation of Alcohol Self-Administration.International journal of molecular sciences · 2024Article
- Complement C3aR signaling: Immune and metabolic modulation and its impact on Alzheimer's disease.European journal of immunology · 2024Review
- Uric Acid Mitigates Cognitive Deficits via TFEB-Mediated Microglial Autophagy in Mice Models of Alzheimer's Disease.Molecular neurobiology · 2024Article
- Impact of TRPV1 on Pathogenesis and Therapy of Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2023Review
- Metabolic regulation of microglial phagocytosis: Implications for Alzheimer's disease therapeutics.Translational neurodegeneration · 2023Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAge is the strongest risk factor for the development of Alzheimer's disease (AD). Besides the pathological hallmarks of β-amyloid (Aβ) plaques and neurofibrillary tangles, emerging evidence demonstrates a critical role of microglia and neuroinflammation in AD pathogenesis. Oleoylethanolamide (OEA) is an endogenous lipid amide that has been shown to promote lifespan and healthspan in C. elegans through regulation of lysosome-to-nucleus signaling and cellular metabolism. The goal of our study was to determine the role of OEA in the mediation of microglial activity and AD pathology using its stable analog, KDS-5104.
methodsWe used primary microglial cultures and genetic and pharmacological approaches to examine the signaling mechanisms and functional roles of OEA in mediating Aβ phagocytosis and clearance, lipid metabolism and inflammasome formation. Further, we tested the effect of OEA in vivo in acute LPS-induced neuroinflammation and by chronic treatment of 5xFAD mice.
resultsWe found that OEA activates PPARα signaling and its downstream cell-surface receptor CD36 activity. In addition, OEA promotes TFEB lysosomal function in a PPARα-dependent but mTORC1-independent manner, the combination of which leads to enhanced microglial Aβ uptake and clearance. These are associated with the suppression of LPS-induced lipid droplet accumulation and inflammasome activation. Chronic treatment of 5xFAD mice with KDS-5104 restored dysregulated lipid profiles, reduced reactive gliosis and Aβ pathology and rescued cognitive impairments.
conclusionTogether, our study provides support that augmenting OEA-mediated lipid signaling may offer therapeutic benefit against aging and AD through modulating lipid metabolism and microglia phagocytosis and clearance.
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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.