Impaired Antioxidant KEAP1-NRF2 System in Amyotrophic Lateral Sclerosis: NRF2 Activation As a Potential Therapeutic Strategy

Overview

Journal Mol Neurodegener

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2021 Oct 19

PMID 34663413

Citations 19

Authors

Silvia Bono

Marco Feligioni

Massimo Corbo

Affiliations

Soon will be listed here.

Abstract

Background: Oxidative stress (OS) is an imbalance between oxidant and antioxidant species and, together with other numerous pathological mechanisms, leads to the degeneration and death of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS).

Main Body: Two of the main players in the molecular and cellular response to OS are NRF2, the transcription nuclear factor erythroid 2-related factor 2, and its principal negative regulator, KEAP1, Kelch-like ECH (erythroid cell-derived protein with CNC homology)-associated protein 1. Here we first provide an overview of the structural organization, regulation, and critical role of the KEAP1-NRF2 system in counteracting OS, with a focus on its alteration in ALS. We then examine several compounds capable of promoting NRF2 activity thereby inducing cytoprotective effects, and which are currently in different stages of clinical development for many pathologies, including neurodegenerative diseases.

Conclusions: Although challenges associated with some of these compounds remain, important advances have been made in the development of safer and more effective drugs that could actually represent a breakthrough for fatal degenerative diseases such as ALS.

Citing Articles

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Upregulated miR-10b-5p as a potential miRNA signature in amyotrophic lateral sclerosis patients.

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