Cited by 290Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsRNA and protein synthesis mechanisms

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Translation of the Alzheimer Amyloid Precursor Protein mRNA Is Up-regulated by Interleukin-1 through 5′-Untranslated Region Sequences

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Rogers, Jack T., Leiter, Lorene M., McPhee, Jay, Cahill, Catherine M., Zhan, Shan-Shan, Potter, Huntington, Nilsson, Lars N.G.·1999·Journal of Biological Chemistry

DOI 10.1074/jbc.274.10.6421

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Abstract

The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD.

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Additional file 5 of Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition
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Additional file 3 of Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition
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Additional file 2 of Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition
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Additional file 1 of Deterioration of cognitive function after transient cerebral ischemia with amyloid-β infusion—possible amelioration of cognitive function by AT2 receptor activation
Min, L.-J., Iwanami, J., Shudou, M., Bai, H.-Y., Shan, B.-S., Higaki, A., Mogi, M., & Horiuchi, M. (2020) · Figshare · doi:10.6084/m9.figshare.12097464
Additional file 1 of Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition
Flores-Aguilar, L., Iulita, M. F., Orciani, C., Tanna, N., Yang, J., Bennett, D. A., & Cuello, A. C. (2021) · Figshare · doi:10.6084/m9.figshare.14908144
Anti-Amyloidogenic, Anti-Inflammatory, and Antioxidant Effects of a Lyposomal Form of Curcumin and MicroRNA-101 in the Experimental Model of Alzheimer’s Disease in Rats
Sokolik, V. V., Berchenko, O. H., Левічева, Н. О., Kot, Y. G., Kot, K., Tigunova, O., Blume, Y. B., & Shulga, S. (2026) · Cytology and Genetics · doi:10.3103/s0095452726010123
Small-Molecule Targeting of the Iron-Responsive Element in the APP mRNA 5′-UTR to Control Amyloid Translation in Alzheimer’s Disease
Khan, M. A., & Shaibah, H. S. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27093978
The TREM2 R47H variant is associated with liver-plasma-brain axis dyshomeostasis in the 5xFAD mouse model of Alzheimer’s disease
Faraci, G., Goodfriend, B., Bishop, J., Vu, M., Avelar‐Barragan, J., Dunham, S. J. B., Rothman, J. A., Whiteson, K., Cheema, A. K., Milinkeviciute, G., et al. (2026) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2026.04.007
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Piłat, D., Baranger, K., & Rivera, S. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2026.07.004
Deciphering the Role of Cytokines in Neuroinflammation
Nagori, K., Sharma, R., Shukla, A., Deshmukh, R., Banchhor, R., Nakhate, K. T., Pradhan, M., Yadav, K., Sharma, M. K., & Gupta, A. (2026) · Wiley eBooks · doi:10.1002/9781394336241.ch5
Proinflammatory actions of derivatives of the β amyloid precursor protein
Barger, S. W. (2001) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8350-4_8

Authors: Rogers, J. T., Leiter, L. M., McPhee, J., Cahill, C. M., Zhan, S.-S., Potter, H., & Nilsson, L. N. G.
Affiliations: Brigham and Women's Hospital (US)
Massachusetts General Hospital (US)
University of South Florida (US)
Corresponding author: Rogers, Jack T.
ORCID: Rogers, Jack T.
Cahill, Catherine M.
Potter, Huntington
Nilsson, Lars N.G.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1999-03
Volume: 274
Issue: 10
Pages: 6421-6431
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.274.10.6421
OpenAlex: W2149650428
Cited by: 290
References: 66
Citations by year: 2026: 8 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 2 · 2021: 10 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 7 · 2016: 10 · 2015: 5 · 2014: 9 · 2013: 7 · 2012: 13
FWCI: 10.62
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7888 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (6872302)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR29I32717)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: amyloid precursor protein, Alzheimer's disease, interleukin-1, translational regulation, 5' untranslated region, translational enhancer, astrocytes, astrocytoma cells, IL-1α, IL-1β, inflammation, ferritin gene, mRNA translation
MeSH terms: Alzheimer Disease, Astrocytes, Base Sequence, Cells, Cultured, Humans, Interleukin-1, Molecular Sequence Data, RNA, Messenger, Transfection, Protein Biosynthesis, Up-Regulation, Amyloid beta-Protein Precursor

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Translation of the Alzheimer Amyloid Precursor Protein mRNA Is Up-regulated by Interleukin-1 through 5′-Untranslated Region Sequences

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