ArticleMolecular neurobiology2020
Iron Overload Impairs Autophagy: Effects of Rapamycin in Ameliorating Iron-Related Memory Deficits.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Effects of cannabidiol in comparison to hormonal therapy on estrogen decline-induced memory impairments and endocannabinoid system in rats.Journal of neuroendocrinology · 2026Article
- The iron-energy metabolism axis in Alzheimer's pathogenesis: from mechanisms to interventions.Cell death discovery · 2026Review
- Elevated iron levels in tears of patients diagnosed with WDR45 X-linked optic atrophy.Orphanet journal of rare diseases · 2026Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Effects of the AMPAR Antagonist, Perampanel, on Cognitive Function in Rats Exposed to Neonatal Iron Overload.Molecular neurobiology · 2024Article
- Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies.Antioxidants (Basel, Switzerland) · 2024Review
- Brain Iron Homeostasis and Mental Disorders.Antioxidants (Basel, Switzerland) · 2023Review
- Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex-dependent manner.Aging cell · 2023Article
- Acetylated Oligopeptide and N-acetyl cysteine Protected Against Oxidative Stress, Inflammation, Testicular-Blood Barrier Damage, and Testicular Cell Death in Iron-Overload Rat Model.Applied biochemistry and biotechnology · 2023Article
- Deficiency of RAB39B Activates ER Stress-Induced Pro-apoptotic Pathway and Causes Mitochondrial Dysfunction and Oxidative Stress in Dopaminergic Neurons by Impairing Autophagy and Upregulating α-Synuclein.Molecular neurobiology · 2023Article
- Autophagy deficiency exacerbates iron overload induced reactive oxygen species production and apoptotic cell death in skeletal muscle cells.Cell death & disease · 2023Article
- Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis.Frontiers in pharmacology · 2023Article
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Iron Metabolism in Aging and Age-Related Diseases.International journal of molecular sciences · 2022Review
- Ferroptosis: A New Strategy for Cancer Therapy.Frontiers in oncology · 2022Review
- Building a Network of Adverse Outcome Pathways (AOPs) Incorporating the Tau-Driven AOP Toward Memory Loss (AOP429).Journal of Alzheimer's disease reports · 2022Review
- Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide-1 analogsWorld journal of biological chemistry · 2021Review
- Effects of lipoic acid supplementation on age- and iron-induced memory impairment, mitochondrial DNA damage and antioxidant responses.European journal of nutrition · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
Over the years, iron accumulation in specific brain regions has been observed in normal aging and related to the pathogenesis of neurodegenerative disorders. Many neurodegenerative diseases may involve cognitive dysfunction, and we have previously shown that neonatal iron overload induces permanent cognitive deficits in adult rats and exacerbates age-associated memory decline. Autophagy is a catabolic pathway involved in the removal of toxic protein aggregates, which are a hallmark of neurodegenerative events. In the present study, we investigated whether iron accumulation would interfere with autophagy and also sought to determine the effects of rapamycin-induced stimulation of autophagy in attenuating iron-related cognitive deficits. Male Wistar rats received a single daily oral dose of vehicle or iron carbonyl (30 mg/kg) at postnatal days 12-14. In adulthood, they received daily intraperitoneal injections of vehicle or rapamycin (0.25 mg/kg) for 14 days. Results showed that iron given in the neonatal period impaired inhibitory avoidance memory and induced a decrease in proteins critically involved in the autophagy pathway, Beclin-1 and LC3, in the hippocampus. Rapamycin in the adulthood reversed iron-induced memory deficits, decreased the ratio phospho-mTOR/total mTOR, and recovered LC3 II levels in iron-treated rats. Our results suggest that iron accumulation, as observed in neurodegenerative disorders, hinders autophagy, which might play a role in iron-induced neurotoxicity. Rapamycin, by inducing authophagy, was able to ameliorate iron-induced cognitive impairments. These findings support the use of rapamycin as a potential neuroprotective treatment against the cognitive decline associated to neurodegenerative disorders.
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