The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Progress Toward Identification of Protease Activity Involved in Proteolysis of Apolipoprotein E in Human Brain
Abstract
Apolipoprotein E (apoE) genotype is the single most important genetic risk factor for the most common (sporadic) form of Alzheimer's disease (AD). Increasing evidence supports the hypothesis that the presence of the E4 isoform of this cholesterol-binding protein contributes directly to disease risk, age of onset, and severity of the neuropathology. For example, studies in transgenic mice demonstrate that apoE is necessary for the formation of plaques with neuritic pathology. The precise mechanism by which apoE contributes to the disease remains unknown. However, several lines of investigation from a number of laboratories now point to a role for proteolytic fragments of apoE in the formation of both plaques and tangles, the two pathological hallmarks of the disease. In particular, the C-terminal portion of apoE has been implicated in binding to amyloid and is localized to plaques. The N-terminal domain, on the other hand, is neurotoxic in culture and has been localized to, and implicated in the formation of, neurofibrillary tangles. These results suggest that inhibition of apoE proteolysis is a potential therapeutic strategy for AD. Using human brain homogenates, we have determined that proteolysis of apoE is greatest at acidic pH and can be inhibited by compounds targeting aspartic proteases. The feasibility of screening candidate inhibitors is supported by both ELISA and immunoblotting methods. Future studies will use a combination of in vitro and in vivo assays to test the…
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“It has also been recognized that co-deposition of apoE in Aβ plaques promotes focal neurodegeneration in humans and in AD Tg mice [22,29,35].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [35]
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Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028
Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., & Ikeda, K. (1991) · Brain Research · doi:10.1016/0006-8993(91)91092-f · Cited by 1,157
Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050004797 · Cited by 937
Senile dementia of the Alzheimer type
Terry, R. D., & Katzman, R. (1983) · Annals of Neurology · doi:10.1002/ana.410140502 · Cited by 839
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830
Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112130 · Cited by 829
Differential Effects of Apolipoproteins E3 and E4 on Neuronal Growth in Vitro
Nathan, B. P., Bellosta, S., Sanan, D. A., Weisgraber, K. H., Mahley, R. W., & Pitas, R. E. (1994) · Science · doi:10.1126/science.8171342 · Cited by 795
Mahley, R. W., & Ji, Z.-S. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33334-4 · Cited by 693
Apolipoprotein E in animal models of CNS injury and in alzheimer's disease
Poirier, J. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90156-2 · Cited by 637
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Apolipoprotein E: From lipid transport to neurobiology
Hauser, P. S., Narayanaswami, V., & Ryan, R. O. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.09.001 · Cited by 320
Yamazaki, Y., Painter, M. M., Bu, G., & Kanekiyo, T. (2016) · CNS Drugs · doi:10.1007/s40263-016-0361-4 · Cited by 173
Apolipoprotein E and cholesterol in aging and disease in the brain
de Chaves, E. P., Narayanaswami, V., Christoffersen, C., & Nielsen, L. B. (2008) · Future Lipidology · doi:10.2217/17460875.3.5.505 · Cited by 164
Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation
Lanfranco, M. F., Sepulveda, J., Kopetsky, G., & Rebeck, G. W. (2021) · Glia · doi:10.1002/glia.23974 · Cited by 164
Huynh, T.-P. V., Wang, C., Tran, A. C., Tabor, G. T., Mahan, T. E., Francis, C. M., Finn, M. B., Spellman, R., Manis, M., Tanzi, R. E., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0337-1 · Cited by 139
Metadata
- Authors
- Marques, M. A., Owens, P. A., & Crutcher, K. A.
- Affiliations
- University of Cincinnati (US)
- Corresponding author
- Crutcher, Keith A.
- ORCID
- Crutcher, Keith A.
- Venue
- Journal of Molecular Neuroscience
- Published
- 2004
- Volume
- 24
- Issue
- 1
- Pages
- 073-080
- ISSN
- 0895-8696 (ISSN-L)
- OpenAlex
- W2021255192
- Cited by
- 29
- References
- 74
- Citations by year
- 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- apolipoprotein E, Alzheimer's disease, aspartic protease, protease inhibitors, APOE ε4, amyloid plaques, neurofibrillary tangles, human brain, inhibitor screening, transgenic mouse model
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Brain, Drug Evaluation, Preclinical, Enzyme Inhibitors, Humans, Peptide Fragments, Peptide Hydrolases, Neurofibrillary Tangles, Plaque, Amyloid
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