ArticleMolecular neurobiology2024
Gemfibrozil Alleviates Cognitive Impairment by Inhibiting Ferroptosis of Astrocytes via Restoring the Iron Metabolism and Promoting Antioxidant Capacity in Type 2 Diabetes.
Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- Mechanisms and Pathogenesis of Diabetic Cognitive Impairment: A Comprehensive Review.Aging and disease · 2025Pooled it
- Identification of Endometriosis Pathophysiologic-Related Genes Based on Meta-Analysis and Bayesian Approach.International journal of molecular sciences · 2025Pooled it
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
- PPARa-FSP1 axis modulates lipid peroxidation-induced neuronal ferroptosis to promote functional recovery in mouse model of traumatic spinal cord injury.Cellular and molecular life sciences : CMLS · 2026Article
- Mechanisms and therapeutic strategies of ferroptosis in Diabetic-Associated Cognitive Dysfunction: focus on the crosstalk with apoptosis, autophagy, and pyroptosis.Molecular biology reports · 2026Review
- Ferroptosis in diabetes-associated cognitive dysfunction: mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- Research Progress on Pathology, Molecular Mechanisms, and Intervention Strategies of Cognitive Dysfunction Associated with Type 2 Diabetes.International journal of general medicine · 2026Review
- Ferroptosis in diabetes mellitus and its complications: overview of clinical and preclinical research.Cell death discovery · 2025Review
- Astrocyte Lipid Droplet Dynamics Orchestrate Neurological Disorders and Therapeutic Horizons.Small science · 2025Review
- Electroacupuncture improves cognitive function in high-fat diet/streptozocin-induced type 2 diabetic mice by inhibiting autophagy-related ferroptosis.Experimental animals · 2025Article
- Lysosomal acidification impairment in astrocyte-mediated neuroinflammation.Journal of neuroinflammation · 2025Review
- Different Types of Cell Death in Diabetic Neuropathy: A Focus on Mechanisms and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders.Antioxidants (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Diabetes-associated cognitive dysfunction (DACD) is considered a significant complication of diabetes and manifests as cognitive impairment. Astrocytes are vital to the brain energy metabolism and cerebral antioxidant status. Ferroptosis has been implicated in cognitive impairment, but it is unclear whether the ferroptosis of astrocytes is involved in the progression of DACD. PPARA/PPARα (peroxisome proliferator-activated receptor alpha) is a transcription factor that regulates glucose and lipid metabolism in the brain. In this study, we demonstrated that high glucose promoted ferroptosis of astrocytes by disrupting iron metabolism and suppressing the xCT/GPX4-regulated pathway in diabetic mice and astrocytes cultured in high glucose. Administration of gemfibrozil, a known PPARα agonist, inhibited ferroptosis and improved memory impairment in db/db mice. Gemfibrozil also prevented the accumulation of lipid peroxidation products and lethal reactive oxygen species induced by iron deposition in astrocytes and substantially reduced neuronal and synaptic loss. Our findings demonstrated that ferroptosis of astrocytes is a novel mechanism in the development of DACD. Additionally, our study revealed the therapeutic effect of gemfibrozil in preventing and treating DACD by inhibiting ferroptosis.
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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.