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Adv Pharm Bull. 2022;12(3): 466-475.
doi: 10.34172/apb.2022.050
PMID: 35935038
PMCID: PMC9348539
Scopus ID: 85140272061
  Abstract View: 787
  PDF Download: 500
  Full Text View: 70

Review Article

Liver X Receptor as a Possible Drug Target for Blood-Brain Barrier Integrity

Mahsa Eskandari 1 ORCID logo, Ali Awsat Mellati 2* ORCID logo

1 Medical School, Zanjan University of Medical Sciences, Zanjan, Iran.
2 Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
*Corresponding Author: Corresponding Author: Ali Awsat Mellati, Tel: +982433240301, Email: , Email: mellati@zums.ac.ir

Abstract

Purpose: blood-brain barrier (BBB) is made of specialized cells that are responsible for the selective passage of substances directed to the brain. The integrated BBB is essential for precise controlling of the different substances passage as well as protecting the brain from various damages. In this article, we attempted to explain the role of liver X receptor (LXR) in maintaining BBB integrity as a possible drug target.

Methods: In this study, various databases, including PubMed, Google Scholar, and Scopus were searched using the following keywords: blood-brain barrier, BBB, liver X receptor, and LXR until July, 2020. Additionally, contents close to the subject of our study were surveyed.

Results: LXR is a receptor the roles of which in various diseases have been investigated. LXR can affect maintaining BBB by affecting various ways such as ATP-binding cassette transporter A1 (ABCA1), matrix metalloproteinase-9 (MMP9), insulin-like growth factor 1 (IGF1), nuclear factor-kappa B (NF-κB) signaling, mitogen-activated protein kinase (MAPK), tight junction molecules, both signal transducer and activator of transcription 1 (STAT1), Wnt/β-catenin Signaling, transforming growth factor beta (TGF-β) signaling, and expressions of Smad 2/3 and Snail.

Conclusion: LXR could possibly be used either as a target for drug delivery to brain tissue or as a target for maintaining the BBB integrity in different diseases; thereby the drug will be conducted to tissues, other than the brain. If it is verified that only LXRα is necessary for protecting BBB, some specific LXRα ligands must be found and then used in medication.

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Submitted: 30 May 2021
Accepted: 13 Aug 2021
ePublished: 14 Aug 2021
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