ArticleBrain pathology (Zurich, Switzerland)2019
The sterol regulatory element-binding protein 2 is dysregulated by tau alterations in Alzheimer disease.
Article in Brain pathology (Zurich, Switzerland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Translatability of Animal Models for Alzheimer's Disease Using a Machine Learning Based Workflow.Clinical and translational science · 2025Article
- Alzheimer's disease pathogenesis: standing at the crossroad of lipid metabolism and immune response.Molecular neurodegeneration · 2025Review
- Genome-wide scan of Flortaucipir PET levels findsmedRxiv : the preprint server for health sciences · 2024Article
- Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer's Disease.Molecular neurobiology · 2023Review
- Aerobic Exercise Facilitates the Nuclear Translocation of SREBP2 by Activating AKT/SEC24D to Contribute Cholesterol Homeostasis for Improving Cognition in APP/PS1 Mice.International journal of molecular sciences · 2023Article
- Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise.The FEBS journal · 2023Review
- Co-expression network analysis of human tau-transgenic mice reveals protein modules associated with tau-induced pathologies.iScience · 2022Article
- Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice.Nutrients · 2022Article
- CREB1ACS omega · 2021Article
- Key Disease Mechanisms Linked to Alzheimer's Disease in the Entorhinal Cortex.International journal of molecular sciences · 2021Article
- Alzheimer's Disease, a Lipid Story: Involvement of Peroxisome Proliferator-Activated Receptor α.Cells · 2020Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
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Abstract
Disturbed neuronal cholesterol homeostasis has been observed in Alzheimer disease (AD) and contributes to the pathogenesis of AD. As the master switch of cholesterol biosynthesis, the sterol regulatory element-binding protein 2 (SREBP-2) translocates to the nucleus after cleavage/activation, but its expression and activation have not been studied in AD which is the focus of the current study. We found both a significant decrease in the nuclear translocation of N-terminal SREBP-2 accompanied by a significant accumulation of C-terminal SREBP-2 in NFT-containing pyramidal neurons in AD. N-terminal- SREBP-2 is also found in dystrophic neurites around plaques in AD brain. Western blot confirmed a significantly reduced nuclear translocation of mature SREBP-2 (mSREBP-2) in AD brain. Interestingly, reduced nuclear mSREBP-2 was only found in animal models of tauopathies such as 3XTg AD mice and P301L Tau Tg mice but not in CRND8 APP transgenic mice, suggesting that tau alterations likely are involved in the changes of mSREBP-2 distribution and activation in AD. Altogether, our study demonstrated disturbed SREBP-2 signaling in AD and related models, and proved for the first time that tau alterations contribute to disturbed cholesterol homeostasis in AD likely through modulation of nuclear mSREBP-2 translocation.
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