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REVIEW article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1437939

Targeting the NRF2 Pathway for Disease Modification in Neurodegenerative diseases: Mechanisms and Therapeutic Implications

Provisionally accepted
Clara Mayer Clara Mayer 1Lluis Riera-Ponsati Lluis Riera-Ponsati 1,2Henrik Klitgaard Henrik Klitgaard 1*Sakari Kauppinen Sakari Kauppinen 1,2*Janine Erler Janine Erler 1*Stine N. Hansen Stine N. Hansen 1*
  • 1 Neumirna Therapeutics Aps, Copenhagen, Denmark
  • 2 Center for RNA Medicine, Aalborg University, Copenhagen, Denmark

The final, formatted version of the article will be published soon.

    Neurodegenerative diseases constitute a global health issue and a major economic burden. They significantly impair both cognitive and motor functions, and their prevalence is expected to rise due to ageing societies and continuous population growth. Conventional therapies provide symptomatic relief, nevertheless, disease-modifying treatments that reduce or halt neuron death and malfunction are still largely unavailable. Amongst the common hallmarks of neurodegenerative diseases are protein aggregation, oxidative stress, neuroinflammation and mitochondrial dysfunction. Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) constitutes a central regulator of cellular defense mechanisms, including the regulation of antioxidant, anti-inflammatory and mitochondrial pathways, making it a highly attractive therapeutic target for disease modification in neurodegenerative disorders.Here, we describe the role of NRF2 in the common hallmarks of neurodegeneration, review the current pharmacological interventions and their challenges in activating the NRF2 pathway, and present alternative therapeutic approaches for disease modification.

    Keywords: Nrf2, BACH1, KEAP1, Oxidative Stress, neurodegeneration, Neuroinflammation, Mitochondrial dysfunction

    Received: 24 May 2024; Accepted: 03 Jul 2024.

    Copyright: © 2024 Mayer, Riera-Ponsati, Klitgaard, Kauppinen, Erler and Hansen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Henrik Klitgaard, Neumirna Therapeutics Aps, Copenhagen, Denmark
    Sakari Kauppinen, Neumirna Therapeutics Aps, Copenhagen, Denmark
    Janine Erler, Neumirna Therapeutics Aps, Copenhagen, Denmark
    Stine N. Hansen, Neumirna Therapeutics Aps, Copenhagen, Denmark

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.