Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity
Open accessAbstract
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.
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The 22 kDa amino-terminal fragment produced by thrombin cleavage (amino acid 1dues) also has neurotoxic effects.
“Additionally, the 22 kDa amino-terminal fragment produced by thrombin cleavage (amino acid 1dues) also has neurotoxic effects (Tolar et al., 1999).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Tolar et al., 1999
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Self-citation
- Authors
- Tolar, M., Keller, J. N., Chan, S., Mattson, M. P., Marques, M. A., & Crutcher, K. A.
- Affiliations
- University of Cincinnati (US)
- University of Kentucky (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-08-15
- Volume
- 19
- Issue
- 16
- Pages
- 7100-7110
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782866
- OpenAlex
- W2097039472
- Cited by
- 148
- References
- 3
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- University of Cincinnati
- National Institutes of Health (NS31410)
- National Institute of Neurological Disorders and Stroke (NS29001, R01NS029001, NS 31410, NS30583, R01NS031410, R01NS030583)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- apolipoprotein E, intracellular calcium, calcium influx, hippocampal neurons, neuronal cell death, NMDA receptor, MK-801, receptor-associated protein, protease inhibitors, Alzheimer's disease
- MeSH terms
- Animals, Apolipoproteins E, Calcium, Cells, Cultured, Chick Embryo, Hippocampus, Humans, Neurotoxins, Peptide Fragments, Protease Inhibitors, Stimulation, Chemical, Dizocilpine Maleate, Cell Death, Excitatory Amino Acid Antagonists, Rats
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