ArticleThe Journal of biological chemistry2015
Activation of peroxisome proliferator-activated receptor α induces lysosomal biogenesis in brain cells: implications for lysosomal storage disorders.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 128 citations in OpenAlex.
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- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Overview of the Zinc Functional Interactome Through Health Hallmarks and Medical Conditions.Nutrients · 2026Review
- Corrected Version: Sodium Benzoate, A Metabolite of Cinnamon and A Food Additive, Improves Cognitive Functions in Mice After Controlled Cortical Impact Injury.Journal of clinical & experimental immunology · 2026Article
- Prospect of Muscle-Building Supplement HMB in Alzheimer's Disease.Journal of clinical & experimental immunology · 2026Article
- Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases.npj aging · 2025Review
- Liver CYP4A autophagic lysosomal degradation: A major role for the autophagic receptor SQSTM1/p62 through an uncommon target interaction site.Molecular pharmacology · 2025Article
- Autophagy and the peroxisome proliferator-activated receptor signaling pathway: A molecular ballet in lipid metabolism and homeostasis.Molecular and cellular biochemistry · 2025Review
- Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation.Nature cell biology · 2025Article
- Epigenetic characterization of adult rhesus monkey spermatogonial stem cells identifies key regulators of stem cell homeostasis.Nucleic acids research · 2024Article
- Pparα activation stimulates autophagic flux through lipid catabolism-independent route.Fish physiology and biochemistry · 2024Article
- Cinnamic acid, a natural plant compound, exhibits neuroprotection in a mouse model of Sandhoff disease via PPARα.NeuroImmune pharmacology and therapeutics · 2024Article
- Gemfibrozil Alleviates Cognitive Impairment by Inhibiting Ferroptosis of Astrocytes via Restoring the Iron Metabolism and Promoting Antioxidant Capacity in Type 2 Diabetes.Molecular neurobiology · 2024Article
- Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions.Frontiers in pharmacology · 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
- Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Article
- Tau fibrils induce glial inflammation and neuropathology via TLR2 in Alzheimer's disease-related mouse models.The Journal of clinical investigation · 2023Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Lysosomes are ubiquitous membrane-enclosed organelles filled with an acidic interior and are central to the autophagic, endocytic, or phagocytic pathway. In contrast to its classical function as the waste management machinery, lysosomes are now considered to be an integral part of various cellular signaling processes. The diverse functionality of this single organelle requires a very complex and coordinated regulation of its activity with transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, at its core. However, mechanisms by which TFEB is regulated are poorly understood. This study demonstrates that gemfibrozil, an agonist of peroxisome proliferator-activated receptor (PPAR) α, alone and in conjunction with all-trans-retinoic acid is capable of enhancing TFEB in brain cells. We also observed that PPARα, but not PPARβ and PPARγ, is involved in gemfibrozil-mediated up-regulation of TFEB. Reporter assay and chromatin immunoprecipitation studies confirmed the recruitment of retinoid X receptor α, PPARα, and PGC1α on the PPAR-binding site on the Tfeb promoter as well. Subsequently, the drug-mediated induction of TFEB caused an increase in lysosomal protein and the lysosomal abundance in cell. Collectively, this study reinforces the link between lysosomal biogenesis and lipid metabolism with TFEB at the crossroads. Furthermore, gemfibrozil may be of therapeutic value in the treatment of lysosomal storage disorders in which autophagy-lysosome pathway plays an important role.
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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.