ArticleJCI insight2021
Regulation of PPARα by APP in Alzheimer disease affects the pharmacological modulation of synaptic activity.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies.Biomedicines · 2025Review
- Targeting PPARs in the Brain: From Old Knowledge to Emerging Therapeutic Roles.CNS & neurological disorders drug targets · 2025Article
- Exploring fatty acid metabolism in Alzheimer's disease: the key role of CPT1A.Scientific reports · 2024Article
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Article
- Early biomarkers in the presymptomatic phase of cognitive impairment: changes in the endocannabinoidome and serotonergic pathways in Alzheimer's-prone mice after mTBI.Acta neuropathologica communications · 2024Article
- Current View on PPAR-α and Its Relation to Neurosteroids in Alzheimer's Disease and Other Neuropsychiatric Disorders: Promising Targets in a Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Article
- Conquering Insulin Network Dysfunctions in Alzheimer's Disease: Where Are We Today?Journal of Alzheimer's disease : JAD · 2024Review
- Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.Nutrients · 2023Review
- Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer's disease at CPT1A locus.Clinical epigenetics · 2023Article
- Oleoylethanolamide facilitates PPARα and TFEB signaling and attenuates Aβ pathology in a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2023Article
- Rise and fall of peroxisomes during Alzheimer´s disease: a pilot study in human brains.Acta neuropathologica communications · 2023Article
- Article
- PPARα Signaling: A Candidate Target in Psychiatric Disorder Management.Biomolecules · 2022Review
- PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among genetic susceptibility loci associated with late-onset Alzheimer disease (LOAD), genetic polymorphisms identified in genes encoding lipid carriers led to the hypothesis that a disruption of lipid metabolism could promote disease progression. We previously reported that amyloid precursor protein (APP) involved in Alzheimer disease (AD) physiopathology impairs lipid synthesis needed for cortical networks' activity and that activation of peroxisome proliferator-activated receptor α (PPARα), a metabolic regulator involved in lipid metabolism, improves synaptic plasticity in an AD mouse model. These observations led us to investigate a possible correlation between PPARα function and full-length APP expression. Here, we report that PPARα expression and activation were inversely related to APP expression both in LOAD brains and in early-onset AD cases with a duplication of the APP gene, but not in control human brains. Moreover, human APP expression decreased PPARA expression and its related target genes in transgenic mice and in cultured cortical cells, while opposite results were observed in APP-silenced cortical networks. In cultured neurons, APP-mediated decrease or increase in synaptic activity was corrected by a PPARα-specific agonist and antagonist, respectively. APP-mediated control of synaptic activity was abolished following PPARα deficiency, indicating a key function of PPARα in this process.
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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 Socratic graph.