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

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

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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Crossref · 10.1074/jbc.274.10.6421

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  • Inflammatory proteins such as interleukin-1β, tumor necrosis factor-α, and interferon-γ can alter APP expression, APP processing, or Aβ transport.

    “Because inflammatory proteins (e.g., interleukin-1β, tumor necrosis factor–α, and interferon-γ) can alter APP expression, APP processing, or Aβ transport (47–50), the inflammatory changes caused by the deletion of Abi3 locus may have contributed to the increase in APP protein level and subsequently Aβ accumulation.”

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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.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-03
Volume
274
Issue
10
Pages
6421-6431
ISSN
0021-9258 (ISSN-L)
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
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
  • Health Sciences › Medicine › Physiology › 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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