Transcription factor Sp1 dysregulation in Alzheimer's disease
Abstract
Altered gene expression occurs in central nervous system disorders, including Alzheimer's disease (AD). Transcription factor Sp1 may be involved insofar as it can regulate the expression of several AD‐related proteins, including amyloid precursor protein (APP) and tau. Sp1 could itself be regulated by inflammatory and other factors associated with AD, such as interleukin‐1β. We measured an almost threefold elevation in the number of mRNA molecules of this cytokine in the AD frontal cortex. Sp1 mRNA was found to be up‐regulated in these AD brains (along with Sp1‐regulated COX‐2), and the Sp1 increase was also seen at the protein level by Western immunoblotting. To determine whether this would also occur in transgenic mice developing AD pathology, we examined the expression of Sp1 in the cortex and hippocampus and observed higher levels of Sp1 mRNA and protein. These results indicate that elements of regulatory pathways involving transcription factor Sp1 may be useful targets for therapeutic intervention to prevent or reverse AD. © 2008 Wiley‐Liss, Inc.
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SP1, a transcription factor that regulates the expression of several amyloid and tau-related genes, has been found to be abnormally expressed in the frontal cortex and hippocampus of patients with AD.
“It is noteworthy that SP1, a transcription factor that regulates the expression of several amyloid and tau-related genes,47 has been found to be abnormally expressed in the frontal cortex and hippocampus of patients with AD.48”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [47]
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APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease
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- Authors
- Citron, B. A., Dennis, J. S., Zeitlin, R. S., & Echeverria, V.
- Affiliations
- University of South Florida (US)
- Bay Pines VA Healthcare System (US)
- Corresponding author
- Citron, Bruce A.
- ORCID
- Citron, Bruce A.
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2008-04-30
- Volume
- 86
- Issue
- 11
- Pages
- 2499-2504
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W1999973557
- Cited by
- 116
- References
- 41
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 9 · 2013: 6 · 2012: 1
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- H. Lee Moffitt Cancer Center and Research Institute
- University of South Florida
- Moffitt Cancer Center
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Sp1, Alzheimer's disease, amyloid precursor protein, tau protein, IL-1β, cyclooxygenase-2, gene expression dysregulation, frontal cortex, hippocampus, transgenic mouse model, neuroinflammation, therapeutic target
- MeSH terms
- Aged, Alzheimer Disease, Animals, Brain, Humans, Mice, Transgenic, RNA, Messenger, Blotting, Western, Up-Regulation, Gene Expression, Sp1 Transcription Factor, Reverse Transcriptase Polymerase Chain Reaction, Mice, Interleukin-1beta
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