The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.
SIRT1 Protects against Microglia-dependent Amyloid-β Toxicity through Inhibiting NF-κB Signaling
Open accessAbstract
Accumulating evidence suggests that neurodegeneration induced by pathogenic proteins depends on contributions from surrounding glia. Here we demonstrate that NF-kappaB signaling in microglia is critically involved in neuronal death induced by amyloid-beta (Abeta) peptides, which are widely presumed to cause Alzheimer disease. Constitutive inhibition of NF-kappaB signaling in microglia by expression of the nondegradable IkappaBalpha superrepressor blocked neurotoxicity, indicating a pivotal role for microglial NF-kappaB signaling in mediating Abeta toxicity. Stimulation of microglia with Abeta increased acetylation of RelA/p65 at lysine 310, which regulates the NF-kappaB pathway. Overexpression of SIRT1 deacetylase and the addition of the SIRT1 agonist resveratrol markedly reduced NF-kappaB signaling stimulated by Abeta and had strong neuroprotective effects. Our results support a glial loop hypothesis by demonstrating a critical role for microglial NF-kappaB signaling in Abeta-dependent neurodegeneration. They also implicate SIRT1 in this pathway and highlight the therapeutic potential of resveratrol and other sirtuin-activating compounds in Alzheimer disease.
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“In a recent study it was found that over expression of SIRT1 deacetylase and SIRT1 activation by resveratrol significantly protects against microglia-dependent amyloid-β toxicity by inhibiting NF-kB signaling199.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [199]
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Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
Sirtuins in mammals: insights into their biological function
Michán, S., & Sinclair, D. A. (2007) · Biochemical Journal · doi:10.1042/bj20070140 · Cited by 1,750
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295
Kim, D., Nguyen, M. D., Dobbin, M. M., Fischer, A., Sananbenesi, F., Rodgers, J. T., Delalle, I., Baur, J. A., Sui, G., Armour, S. M., et al. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601758 · Cited by 1,074
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
Min, S.-W., Cho, S.-H., Zhou, Y., Schroeder, S., Haroutunian, V., Seeley, W. W., Huang, E. J., Shen, Y., Masliah, E., Mukherjee, C., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.044 · Cited by 949
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Metadata
- Authors
- Chen, J., Zhou, Y., Mueller-Steiner, S., Chen, L.-F., Kwon, H., Yi, S., Mucke, L., & Gan, L.
- Affiliations
- Gladstone Institutes (US)
- Corresponding author
- Gan, Li
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 280
- Issue
- 48
- Pages
- 40364-40374
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2074916731
- Cited by
- 740
- References
- 54
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 35 · 2023: 36 · 2022: 22 · 2021: 39 · 2020: 49 · 2019: 30 · 2018: 46 · 2017: 40 · 2016: 26 · 2015: 35 · 2014: 35 · 2013: 48 · 2012: 43
- FWCI
- 17.20
- 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
- University of California, San Francisco
- National Institute of Neurological Disorders and Stroke (NS43945, R01NS043945)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- SIRT1, microglia, amyloid-beta, NF-κB signaling, Alzheimer's disease, neurodegeneration, resveratrol, neuroprotection
- MeSH terms
- Resveratrol, Alzheimer Disease, Animals, Bromodeoxyuridine, Cells, Cultured, Genetic Vectors, Humans, Immunohistochemistry, Lysine, Microscopy, Fluorescence, Models, Biological, Models, Genetic, Neurons, Stilbenes, Signal Transduction, Lentivirus, Amyloid beta-Peptides, NF-kappa B, Rats, Sprague-Dawley, Microglia, Genes, Reporter, Reverse Transcriptase Polymerase Chain Reaction, Sirtuins, Green Fluorescent Proteins, Rats, Sirtuin 1
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