Nrf2: a dark horse in Alzheimer's disease treatment

Alsiddig Osama; Junmin Zhang; Juan Yao; Xiaojun Yao; Jianguo Fang

doi:10.1016/j.arr.2020.101206

Nrf2: a dark horse in Alzheimer's disease treatment

Ageing Res Rev. 2020 Dec:64:101206. doi: 10.1016/j.arr.2020.101206. Epub 2020 Nov 2.

Authors

Alsiddig Osama¹, Junmin Zhang², Juan Yao³, Xiaojun Yao⁴, Jianguo Fang⁵

Affiliations

¹ State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
² State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
³ School of pharmacy, Gansu University of Chinese Medicine, Lanzhou, 730000, China.
⁴ State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. Electronic address: xjyao@lzu.edu.cn.
⁵ State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China. Electronic address: fangjg@lzu.edu.cn.

PMID: 33144124
DOI: 10.1016/j.arr.2020.101206

Abstract

Alzheimer's disease (AD), an age-dependent neurodegenerative disorder, is the main cause of dementia. Common hallmarks of AD include the amyloid β-peptide (Aβ) aggregation, high levels of hyperphosphorylated tau protein (p-tau) and failure in redox homeostasis. To date, all proposed drugs affecting Aβ and/or p-tau have been failed in clinical trials. A decline in the expression of the transcription factor Nrf2 (nuclear factor-erythroid 2-p45 derived factor 2) and its driven genes (NQO1, HO-1, and GCLC), and alteration of the Nrf2-related pathways have been observed in AD brains. Nrf2 plays a critical role in maintaining cellular redox homeostasis and regulating inflammation response. Nrf2 activation also provides cytoprotection against increasing pathologies including neurodegenerative diseases. These lines of evidence imply that Nrf2 activation may be a novel AD treatment option. Interestingly, recent studies have also demonstrated that Nrf2 interferes with several key pathogenic processes in AD including Aβ and p-tau pathways. The current review aims to provide insights into the role of Nrf2 in AD. Also, we discuss the progress and challenges regarding the Nrf2 activators for AD treatment.

Keywords: Alzheimer's disease; Amyloid β-peptide; Keap1; Nrf2; Oxidative Stress; Tau protein.

Publication types

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

MeSH terms

Alzheimer Disease* / drug therapy
Amyloid beta-Peptides / metabolism
Gene Expression Regulation
Humans
NF-E2-Related Factor 2 / metabolism
Oxidation-Reduction

Substances

Amyloid beta-Peptides
NF-E2-Related Factor 2