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REVIEW article
Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1551571
This article is part of the Research TopicProteostasis disruption in neurodegenerative disorders: Mechanisms and treatment strategiesView all 3 articles
NFE2L1 as a Central Regulator of Proteostasis in Neurodegenerative Diseases: Interplay with Autophagy, Ferroptosis, and the Proteasome
Provisionally accepted- 1Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland
- 2Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute (PAS), Warsaw, Masovian, Poland
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Maintaining proteostasis is critical for neuronal health, with its disruption underpinning the progression of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Nuclear Factor Erythroid 2-Related Factor 1 (NFE2L1) has emerged as a key regulator of proteostasis, integrating proteasome function, autophagy, and ferroptosis to counteract oxidative stress and protein misfolding. This review synthesizes current knowledge on the role of NFE2L1 in maintaining neuronal homeostasis, focusing on its mechanisms for mitigating proteotoxic stress and supporting cellular health offering protection against neurodegeneration. Furthermore, we discuss the pathological implications of NFE2L1 dysfunction and explore its potential as a therapeutic target. By highlighting gaps in the current understanding and presenting future research directions, this review aims to elucidate NFE2L1’s role in advancing treatment strategies for neurodegenerative diseases.
Keywords: Nfe2l1, proteostasis, Neurodegenerative Diseases, Autophagy, ferroptosis, Proteasome, Oxidative Stress, mitochondrial health List Paragraph
Received: 25 Dec 2024; Accepted: 14 Mar 2025.
Copyright: © 2025 Khodadadi, Łuczyńska, Winiarczyk, Leszczyński and Taniguchi. 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: Hiroaki Taniguchi, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland
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