ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1999
Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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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, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Apolipoprotein E Gene Polymorphisms Are Risk Factors for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis.Current medical science · 2019Pooled it
- Nanomaterial strategies for mitigating protein misfolding and neuroinflammation in neurodegenerative diseases.Zoological research · 2026Review
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- Astrovascular decoupling in awake 5×FAD mice is associated with reduced astrocytic calcium.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Alzheimer's disease phenotype based upon the carrier status of the apolipoprotein E ɛ4 allele.Brain pathology (Zurich, Switzerland) · 2024Review
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Are apolipoprotein E fragments a promising new therapeutic target for Alzheimer's disease?Therapeutic advances in chronic disease · 2022Review
- APOE4 Affects Basal and NMDAR-Mediated Protein Synthesis in Neurons by Perturbing Calcium Homeostasis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- GPR18 drives FAAH inhibition-induced neuroprotection against HIV-1 Tat-induced neurodegeneration.Experimental neurology · 2021Article
- The LDL receptor binding domain of apolipoprotein E directs the relative orientation of its C-terminal segment in reconstituted nascent HDL.Biochimica et biophysica acta. Biomembranes · 2021Article
- In vivo brain imaging of mitochondrial CaBiochimica et biophysica acta. Molecular cell research · 2021Review
- Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.Frontiers in molecular neuroscience · 2021Review
- Review
- Understanding the Role of ApoE Fragments in Alzheimer's Disease.Neurochemical research · 2019Review
- Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer's disease.Neuropathology and applied neurobiology · 2019Review
- ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenicDisease models & mechanisms · 2019Article
- SK channel activation is neuroprotective in conditions of enhanced ER-mitochondrial coupling.Cell death & disease · 2018Article
- The serine protease HtrA1 contributes to the formation of an extracellular 25-kDa apolipoprotein E fragment that stimulates neuritogenesis.The Journal of biological chemistry · 2018Article
- The role of APOE on lipid homeostasis and inflammation in normal brains.Journal of lipid research · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein E (apoE)-related synthetic peptides, the 22 kDa N-terminal thrombin-cleavage fragment of apoE (truncated apoE), and full-length apoE have all been shown to exhibit neurotoxic activity under certain culture conditions. In the present study, protease inhibitors reduced the neurotoxicity and proteolysis of full-length apoE but did not block the toxicity of truncated apoE or a synthetic apoE peptide, suggesting that fragments of apoE may account for its toxicity. Additional experiments demonstrated that both truncated apoE and the apoE peptide elicit an increase in intracellular calcium levels and subsequent death of embryonic rat hippocampal neurons in culture. Similar effects on calcium were found when the apoE peptide was applied to chick sympathetic neurons. The rise in intracellular calcium and the hippocampal cell death caused by the apoE peptide were significantly reduced by receptor-associated protein, removal of extracellular calcium, or administration of the specific NMDA glutamate receptor antagonist MK-801. These results suggest that apoE may be a source of both neurotoxicity and calcium influx that involves cell surface receptors. Such findings strengthen the hypothesis that apoE plays a direct role in the pathology of Alzheimer's disease.
Indexed as
Identifiers
10436064PMC6782866W2097039472What OpenQuestion holds
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.