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Azizidoost S, Babaahmadi-Rezaei H, Nazeri Z, et al. Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes. Biochim Biophys Acta Mol Cell Biol Lipids. 2021;1867(1):159069doi: 10.1016/j.bbalip.2021.159069.
Azizidoost, S., Babaahmadi-Rezaei, H., Nazeri, Z., Cheraghzadeh, M., & Kheirollah, A. (2022). Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes. Biochimica et biophysica acta. Molecular and cell biology of lipids, 1867(1), 159069. https://doi.org/10.1016/j.bbalip.2021.159069
Azizidoost, Shirin, et al. "Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes." Biochimica et biophysica acta. Molecular and cell biology of lipids vol. 1867,1 (2022): 159069. doi: https://doi.org/10.1016/j.bbalip.2021.159069
Azizidoost S, Babaahmadi-Rezaei H, Nazeri Z, Cheraghzadeh M, Kheirollah A. Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes. Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Jan;1867(1):159069. doi: 10.1016/j.bbalip.2021.159069. Epub 2021 Oct 28. PMID: 34744007.
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Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Jan;1867(1):159069. doi: 10.1016/j.bbalip.2021.159069. Epub 2021 Oct 28.

Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and accumulation in mice neurons and astrocytes.

Biochimica et biophysica acta. Molecular and cell biology of lipids

Shirin Azizidoost, Hossein Babaahmadi-Rezaei, Zahra Nazeri, Maryam Cheraghzadeh, Alireza Kheirollah

Affiliations

  1. Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  2. Department of Biochemistry, Medical School, Cellular & Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  3. Department of Biochemistry, Medical School, Cellular & Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: [email protected].

PMID: 34744007 DOI: 10.1016/j.bbalip.2021.159069

Abstract

INTRODUCTION: Imbalanced cholesterol metabolism in the brain is one of the main pathophysiological mechanisms involved in Alzheimer's disease. We investigated the effect of amyloid-beta (Aβ) on the main proteins involved in regulation of cholesterol metabolism along with cholesterol content in astrocytes and neurons.

METHODS: Astrocytes and neurons were cultured and treated with Aβ. Apolipoprotein E (apoE) level in the cells and conditioned media, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), ATP-binding cassette transporter A1 (ABCA1), and cytochrome P450 46A1 (CYP46A1) in cell lysates were determined using immunoblotting. Astrocyte media was added to the Aβ-pretreated neurons then, HMGCR was assessed. Cholesterol was measured in both cells and media.

RESULTS: Aβ caused a significant increase in HMGCR and ABCA1 protein levels and cholesterol content in both cells without increasing cholesterol efflux. A similar increase was seen for cellular apoE level in astrocytes with no changes in media with a significant reduction of cholesterol efflux. HMGCR level was restored to near control level when Aβ-pretreated neurons were exposed to media from culture astrocytes.

CONCLUSION: Almost all events related to cholesterol homeostasis in neurons and astrocytes, are somehow affected by Aβ. However, because ABCA1 has the most important role(s) in brain cholesterol homeostasis, all subsequent events associated with astrocytes-cholesterol synthesis and its shuttling to neurons are influenced by the effects of Aβ on ABCA1 which could likely be responsible for altered brain cholesterol metabolism in Alzheimer's disease.

Copyright © 2021 Elsevier B.V. All rights reserved.

Keywords: Alzheimer's disease; Amyloid-beta; Astrocytes; Brain apoE; Cholesterol; Neuron

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