Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

Abstract

Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy.

• Authors: Xilin Zhang, Jin Hu, Li Zhong, Na Wang, Longyu Yang, Chia-Chen Liu, Huifang Li, Xin Wang, Ying Zhou, Yunwu Zhang, Huaxi Xu, Guojun Bu, Jiangxing Zhuang
• Journal: Neuropharmacology (Neuropharmacology) Vol. 108 Pg. 179-92 (09 2016) ISSN: 1873-7064 [Electronic] England
• PMID: 27114256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Antioxidants
• Apolipoproteins E
• Quercetin

Topics

• Administration, Oral
• Amyloid beta-Peptides (antagonists & inhibitors, metabolism)
• Animals
• Antioxidants (administration & dosage)
• Apolipoproteins E (antagonists & inhibitors, metabolism)
• Astrocytes (drug effects, metabolism)
• Cell Line, Transformed
• Cerebral Cortex (drug effects, metabolism)
• Female
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Plaque, Amyloid (drug therapy, metabolism)
• Protein Stability (drug effects)
• Quercetin (administration & dosage)