The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Inhibition of energy metabolism alters the processing of amyloid precursor protein and induces a potentially amyloidogenic derivative
Open accessAbstract
The cellular mechanisms which lead to the generation and pathological deposition of beta amyloid in Alzheimer's disease are unknown. In this report we describe the proteolytic processing of the amyloid precursor protein (APP) to an 11.5-kDa COOH-terminal derivative which contains the full-length beta amyloid sequence. This processing step normally occurs at low levels in parallel with APP maturation in the secretory pathway. Inhibition of oxidative energy metabolism by sodium azide or the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone increased the proteolysis of APP to the 11.5-kDa derivative by about 80-fold with accumulation of this APP derivative in the Golgi complex. Agents which inhibit protein transport in the secretory pathway, including monensin and brefeldin A, also increased the production of the 11.5-kDa derivative. Inhibition of APP maturation demonstrated that the 11.5-kDa derivative could be produced by proteolysis of immature APP. These results demonstrate that APP processing to potentially amyloidogenic COOH-terminal derivatives occurs in either the endoplasmic reticulum or Golgi complex and can be modulated by the state of cellular energy metabolism. Deficits in oxidative energy metabolism have recently been found in the cerebral cortex of patients with Alzheimer's disease. These findings raise the possibility that energy-related metabolic stress may lead to altered metabolism of APP and contribute to amyloidosis in Alzheimer's disease.
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In the citing paper
“Data also argue mitochondria directly influence other AD-associated pathologies, and particularly APP and Aβ homeostasis.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [50]
In the citing paper
“Whether Aβ changes precede either age-related or AD-related brain bioenergetic changes is less clear-cut, especially since abundant data from human and cell-based studies either suggest or demonstrate bioenergetic factors regulate both APP processing and Aβ production [95–100].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [95]
In the citing paper
“Whether Aβ changes precede either age-related or AD-related brain bioenergetic changes is less clear-cut, especially since abundant data from human and cell-based studies either suggest or demonstrate bioenergetic factors regulate both APP processing and Aβ production [95–100].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [95]
In the citing paper
“This was directly demonstrated in cell culture experiments in which COX inhibition and ATP depletion both reduced non-amyloidogenic, α secretase-mediated APP processing [95, 96, 98].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [95]
In the citing paper
“Bioenergetic metabolism certainly affects APP processing and Aβ production.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [95]
Citations
Cites
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404
Matsudaira, P. T. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61070-1 · Cited by 4,951
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Amyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921
De Duve, C., De Barsy, T., Poole, B., Trouet, A., Tulkens, P., & Van Hoof, F. (1974) · Biochemical Pharmacology · doi:10.1016/0006-2952(74)90174-9 · Cited by 1,901
Brefeldin A: insights into the control of membrane traffic and organelle structure.
Klausner, R. D., Donaldson, J. G., & Lippincott‐Schwartz, J. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.116.5.1071 · Cited by 1,843
Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., & Selkoe, D. J. (1992) · Nature · doi:10.1038/360672a0 · Cited by 1,757
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731
Research works printed but not linked: 1
- Mutisya, 1993, Abstr. Neurosci., 19, 1474
Cited by
Sorted by citations
Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β
Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., & Yuan, J. (2000) · Nature · doi:10.1038/47513 · Cited by 3,292
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease
Tönnies, E., & Trushina, E. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161088 · Cited by 1,750
Gaggelli, E., Kozlowski, H., Valensin, D., & Valensin, G. (2006) · Chemical Reviews · doi:10.1021/cr040410w · Cited by 1,729
Aging, energy, and oxidative stress in neurodegenerative diseases
Beal, M. F. (1995) · Annals of Neurology · doi:10.1002/ana.410380304 · Cited by 1,434
Metadata
- Authors
- Gabuzda, D., Busciglio, J., Chen, L. B., Matsudaira, P., & Yankner, B. A.
- Affiliations
- Boston Children's Hospital (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-05
- Volume
- 269
- Issue
- 18
- Pages
- 13623-13628
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1580327310
- Cited by
- 373
- References
- 45
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 9 · 2022: 5 · 2021: 14 · 2020: 13 · 2019: 16 · 2018: 14 · 2017: 6 · 2016: 9 · 2015: 9 · 2014: 6 · 2013: 7 · 2012: 11
- FWCI
- 13.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ag009229-05)
- National Institute on Aging (AG09229)
- National Institute of Neurological Disorders and Stroke (R01NS030352, NS30352)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid precursor protein, APP processing, amyloid-beta, Alzheimer's disease, oxidative metabolism, mitochondrial uncoupling, sodium azide, CCCP, Golgi apparatus, secretory pathway, protein trafficking, endoplasmic reticulum, proteolysis, metabolic stress, amyloidosis
- MeSH terms
- Adenosine Triphosphate, Amyloid, Biological Transport, Cells, Cultured, Energy Metabolism, Humans, Hydrolysis, Protein Processing, Post-Translational, Amyloid beta-Protein Precursor
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