Interferon γ stimulates β-secretase expression and sAPPβ production in astrocytes
Abstract
Neurons, but not astrocytes, are known as the major source of Abeta, because astrocytes express low levels of putative beta-secretase (BACE). Astrocytes near senile plaque cores show enhanced levels of BACE protein expression, however, suggesting that astrocytes can contribute to Abeta production under pathological conditions. To investigate factors that stimulate BACE protein expression in astrocytes, we tested the effects of interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) on BACE protein expression in U373MG astrocytoma cells and primary astrocyte cultures from Tg2576 mouse brains. BACE protein expression and sAPPbeta production were dramatically increased, without changes in holo APP levels, following IFN-gamma treatment in both cell types. AG490, which is a blocker of IFN-gamma-induced STAT signaling, decreased IFN-gamma-induced BACE protein expression and sAPPbeta production in a dose-dependent manner. These results show that astrocytes are capable of expressing BACE and producing sAPPbeta in response to certain stimulating factors, and IFN-gamma is one such factor.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Reactive microglia and astrocytes promote neuroinflammation by releasing cytokines and inflammatory factors such as IL-1β and IL-6 in AD.
“Reactive microglia and astrocytes could promote neuroinflammation by releasing cytokines and inflammatory factors such as IL-1β and IL-6 in AD (H. S. Hong et al., 2003).”
From AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin (2024) · cites this paper as H. S. Hong et al., 2003
Cites
Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876 · see citing works
Cytokine production in the central nervous system
Woodroofe, M. N. (1995) · Neurology · doi:10.1212/wnl.45.6_suppl_6.s6 · Cited by 137 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550 · see citing works
He, P., Zhong, Z., Lindholm, K., Berning, L., Lee, W., Lemere, C., Staufenbiel, M., Li, R., & Shen, Y. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200705042 · Cited by 390 · see citing works
Yamamoto, M., Kiyota, T., Horiba, M., Buescher, J. L., Walsh, S. M., Gendelman, H. E., & Ikezu, T. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060378 · Cited by 367 · see citing works
TREM2 and the neuroimmunology of Alzheimer's disease
Hickman, S. E., & El Khoury, J. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.11.021 · Cited by 221 · see citing works
Zhong, Z., Ewers, M., Teipel, S., Bürger, K., Wallin, A., Blennow, K., He, P., McAllister, C., Hampel, H., & Shen, Y. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.6.718 · Cited by 206 · see citing works
Bazan, N. G. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.09.003 · Cited by 148 · see citing works
Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease
Yao, Z., Yang, W., Gao, Z., & Jia, P. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.03.027 · Cited by 140 · see citing works
Avila-Muñoz, E., & Arias, C. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.07.004 · Cited by 114 · see citing works
Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis
Mattsson, N., Axelsson, M., Haghighi, S., Malmeström, C., Wu, G., Anckarsäter, R., Sankaranarayanan, S., Andreasson, U., Fredrikson, S., Gundersen, A., et al. (2009) · Multiple Sclerosis Journal · doi:10.1177/1352458508100031 · Cited by 61 · see citing works
BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens
Hwang, E. M., Ryu, Y. B., Kim, H. Y., Kim, D.-G., Hong, S.-G., Lee, J. H., Curtis-Long, M. J., Jeong, S. H., Park, J.-Y., & Park, K. H. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.05.080 · Cited by 53 · see citing works
Self-citationCholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
Staurenghi, E., Giannelli, S., Testa, G., Sottero, B., Leonarduzzi, G., & Gamba, P. (2021) · Antioxidants · doi:10.3390/antiox10121890 · Cited by 44 · see citing works
Is It the Twilight of BACE1 Inhibitors?
Hrabinova, M., Pejchal, J., Kucera, T., Jun, D., Schmidt, M., & Soukup, O. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200503023323 · Cited by 28 · see citing works
Sun, H., Gao, X., Niu, J., Chen, P., He, S., Xu, S., & Ge, J. (2024) · eneuro · doi:10.1523/eneuro.0310-24.2024 · Cited by 12 · see citing works
- Authors
- Hong, H. S., Hwang, E. M., Sim, H. J., Cho, H.-J., Boo, J. H., Oh, S. S., Kim, S. U., & Mook-Jung, I.
- Affiliations
- Ajou University (KR)
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 307
- Issue
- 4
- Pages
- 922-927
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2024073076
- Cited by
- 81
- References
- 2
- Citations by year
- 2026: 3 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- AJOU Open Repository (Ajou University) (submittedVersion)
- 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
- interferon-gamma, beta-secretase, BACE, sAPPβ, amyloid-beta production, astrocytes, IL-1β, STAT signaling, AG490, amyloid plaques, Alzheimer's disease
- MeSH terms
- Amyloidosis, Animals, Astrocytes, Brain Diseases, Cells, Cultured, Humans, Interferon-gamma, Mice, Mutant Strains, Endopeptidases, Tumor Cells, Cultured, Trans-Activators, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Tyrphostins, Mice, Amyloid Precursor Protein Secretases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
