The novel function of bexarotene for neurological diseases

Yangtao Liu; Pengwei Wang; Guofang Jin; Peijie Shi; Yonghui Zhao; Jiayi Guo; Yaling Yin; Qianhang Shao; Peng Li; Pengfei Yang

doi:10.1016/j.arr.2023.102021

The novel function of bexarotene for neurological diseases

Ageing Res Rev. 2023 Sep:90:102021. doi: 10.1016/j.arr.2023.102021. Epub 2023 Jul 24.

Authors

Yangtao Liu¹, Pengwei Wang², Guofang Jin³, Peijie Shi⁴, Yonghui Zhao⁵, Jiayi Guo³, Yaling Yin⁶, Qianhang Shao⁷, Peng Li⁸, Pengfei Yang⁹

Affiliations

¹ College of Pharamacy, Xinxiang Medical University, Xinxiang, China; Xinxiang Key Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China; College of Third Clinical, Xinxiang Medical University, Xinxiang, China.
² Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Weihui, China.
³ College of Pharamacy, Xinxiang Medical University, Xinxiang, China; Xinxiang Key Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China.
⁴ College of Pharamacy, Xinxiang Medical University, Xinxiang, China; Xinxiang Key Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China; Xinxiang First People's Hospital, The Affiliated People's Hospital of Xinxiang Medical University, Xinxiang, China.
⁵ Xinxiang First People's Hospital, The Affiliated People's Hospital of Xinxiang Medical University, Xinxiang, China.
⁶ School of Basic Medical Sciences, Department of Physiology and Pathophysiology, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, China.
⁷ Department of Pharmacy, People's Hospital of Peking University, Beijing, China. Electronic address: shaoqianhang0322@163.com.
⁸ College of Pharamacy, Xinxiang Medical University, Xinxiang, China; Xinxiang Key Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China. Electronic address: 071021@xxmu.edu.cn.
⁹ College of Pharamacy, Xinxiang Medical University, Xinxiang, China; Xinxiang Key Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development, Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China. Electronic address: 171048@xxmu.edu.cn.

PMID: 37495118
DOI: 10.1016/j.arr.2023.102021

Abstract

Bexarotene, a retinoid X receptor (RXR) agonist, is approved by FDA to treat cutaneous T-cell lymphoma. However, it has also demonstrated promising therapeutic potential for neurological diseases such as stroke, traumatic brain injury, Parkinson's disease, and particularly Alzheimer's disease(AD). In AD, bexarotene inhibits the production and aggregation of amyloid β (Aβ), activates Liver X Receptor/RXR heterodimers to increase lipidated apolipoprotein E to remove Aβ, mitigates the negative impact of Aβ, regulates neuroinflammation, and ultimately improves cognitive function. For other neurological diseases, its mechanisms of action include inhibiting inflammatory responses, up-regulating microglial phagocytosis, and reducing misfolded protein aggregation, all of which aid in alleviating neurological damage. Here, we briefly discuss the characteristics, applications, and adverse effects of bexarotene, summarize its pharmacological mechanisms and therapeutic results in various neurological diseases, and elaborate on the problems encountered in preclinical research, with the aim of providing help for the further application of bexarotene in central nervous system diseases.

Keywords: Alzheimer’s disease; Apolipoprotein E; Bexarotene; Neurodegenerative diseases; Stroke.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / metabolism
Amyloid beta-Peptides* / metabolism
Bexarotene / therapeutic use
Humans
Retinoid X Receptors / agonists
Retinoid X Receptors / metabolism
Retinoid X Receptors / therapeutic use
Tetrahydronaphthalenes / adverse effects

Substances

Bexarotene
Amyloid beta-Peptides
Tetrahydronaphthalenes
Retinoid X Receptors