ArticleThe Journal of biological chemistry2009
Apolipoprotein E4 domain interaction induces endoplasmic reticulum stress and impairs astrocyte function.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 83 citations in OpenAlex.
- Article
- Huntingtin knockdown dysregulates autophagic degradation of Apolipoprotein E.Journal of Huntington's disease · 2026Article
- Type 2 Diabetes Mellitus, Cognitive Performance, and Incident Dementia; Identifying Mediating Pathways and Biomarkers From the Plasma Proteome.Journal of neurochemistry · 2025Article
- The APOE ε4 allele affects the survival of patients with Parkinson's disease independent of dementia.Journal of translational medicine · 2025Article
- Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.Molecular neurobiology · 2025Review
- Multi-functional role of apolipoprotein E in neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.PLoS computational biology · 2024Article
- TRPV1 alleviates APOE4-dependent microglial antigen presentation and T cell infiltration in Alzheimer's disease.Translational neurodegeneration · 2024Article
- Article
- Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.bioRxiv : the preprint server for biology · 2024Article
- Article
- Lipoprotein Metabolism, Protein Aggregation, and Alzheimer's Disease: A Literature Review.International journal of molecular sciences · 2023Review
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Protein synthesis inhibition and loss of homeostatic functions in astrocytes from an Alzheimer's disease mouse model: a role for ER-mitochondria interaction.Cell death & disease · 2022Article
- Review
- The relationships between neuroglial and neuronal changes in Alzheimer's disease, and the related controversies II:Journal of central nervous system disease · 2022Review
- The relationships between neuroglial alterations and neuronal changes in Alzheimer's disease, and the related controversies I: Gliopathogenesis and glioprotection.Journal of central nervous system disease · 2022Review
- Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation.Glia · 2021Article
- The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.Neurobiology of learning and memory · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Domain interaction, a structural property of apolipoprotein E4 (apoE4), is predicted to contribute to the association of apoE4 with Alzheimer disease. Arg-61 apoE mice, a gene-targeted mouse model specific for domain interaction, have lower brain apoE levels and synaptic, functional, and cognitive deficits. We hypothesized that domain interaction elicits an endoplasmic reticulum (ER) stress in astrocytes and an unfolded protein response that targets Arg-61 apoE for degradation. Primary Arg-61 apoE astrocytes had less intracellular apoE than wild-type astrocytes, and unfolded protein response markers OASIS (old astrocyte specifically induced substance), ATF4, and XBP-1 and downstream effectors were up-regulated. ER stress appears to cause global astrocyte dysfunction as glucose uptake was decreased in Arg-61 apoE astrocytes, and astrocyte-conditioned medium promoted neurite outgrowth less efficiently than wild-type medium in Neuro-2a cell cultures. We showed age-dependent up-regulation of brain OASIS levels and processing in Arg-61 apoE mice. ER stress and astrocyte dysfunction represent a new paradigm underlying the association of apoE4 with neurodegeneration.
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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 OpenQuestion graph.