ArticleCell death and differentiation2022
Selective ferroptosis vulnerability due to familial Alzheimer's disease presenilin mutations.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 94 citations in OpenAlex.
- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- N 6 -methyladenosine modification regulates cell death in cognitive impairment.Neural regeneration research · 2026Article
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Advances in nano-TCM for Alzheimer's disease: lipid-based carriers integrated with innovative delivery strategies.Journal of nanobiotechnology · 2026Review
- Interactions between the gut microbiome and ferroptosis in degenerative diseases: Novel mechanisms and potential therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- miRNA-Mediated Regulation of Ferroptosis in Neurological Disorders: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Targeting the Gut-Brain-Ferroptosis Axis: Molecular Mechanisms and Therapeutic Potential in Alzheimer's Disease and Epilepsy.Journal of molecular neuroscience : MN · 2026Review
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Review
- Ferroptosis and Alzheimer's disease: a new insight into neurodegeneration.Frontiers in immunology · 2026Review
- Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- Pre-activation of T cell immunity potentiates ferroptotic cell death through arachidonic acid hybridized nanovesicles.Journal of nanobiotechnology · 2025Article
- Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neuroferroptosis in health and diseases.Nature reviews. Neuroscience · 2025Review
- Proteomic Investigation of Neurotrophic trans-Banglene Reveals Potential Link to Iron Homeostasis.Molecular neurobiology · 2025Article
- MiR-7a-Klf4 axis as a regulator and therapeutic target of neuroinflammation and ferroptosis in Alzheimer's disease.NAR molecular medicine · 2025Article
- CRISPR screen reveals a simultaneous targeted mechanism to reduce cancer cell selenium and increase lipid oxidation to induce ferroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Exploring the co-morbid relationship between Alzheimer's disease and lung cancer in the 5xFAD transgenic mouse model.Animal models and experimental medicine · 2025Article
- Apolipoprotein E in Alzheimer's disease: molecular insights and therapeutic opportunities.Molecular neurodegeneration · 2025Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in presenilin 1 and 2 (PS1 and PS2) cause autosomal dominant familial Alzheimer's disease (FAD). Ferroptosis has been implicated as a mechanism of neurodegeneration in AD since neocortical iron burden predicts Alzheimer's disease (AD) progression. We found that loss of the presenilins dramatically sensitizes multiple cell types to ferroptosis, but not apoptosis. FAD causal mutations of presenilins similarly sensitizes cells to ferroptosis. The presenilins promote the expression of GPX4, the selenoprotein checkpoint enzyme that blocks ferroptosis by quenching the membrane propagation of lethal hydroperoxyl radicals. Presenilin γ-secretase activity cleaves Notch-1 to signal LRP8 expression, which then controls GPX4 expression by regulating the supply of selenium into the cell since LRP8 is the uptake receptor for selenoprotein P. Selenium uptake is thus disrupted by presenilin FAD mutations, suppressing GPX4 expression. Therefore, presenilin mutations may promote neurodegeneration by derepressing ferroptosis, which has implications for disease-modifying therapeutics.
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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.