Cited by 297Genomics, phytochemicals, and oxidative stressNuclear Receptors and SignalingEndoplasmic Reticulum Stress and Disease

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NRF2 as a Therapeutic Target in Neurodegenerative Diseases

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Brandes, Mikah S., Gray, Nora E.·2020·ASN Neuro

DOI 10.1177/1759091419899782PMC PMC6977098

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Abstract

Increased reactive oxygen species production and oxidative stress have been implicated in the pathogenesis of numerous neurodegenerative conditions including among others Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Friedrich’s ataxia, multiple sclerosis, and stroke. The endogenous antioxidant response pathway protects cells from oxidative stress by increasing the expression of cytoprotective enzymes and is regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). In addition to regulating the expression of antioxidant genes, NRF2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. This is because mitochondrial dysfunction and neuroinflammation are features of many neurodegenerative diseases as well NRF2 has emerged as a promising therapeutic target. Here, we review evidence for a beneficial role of NRF2 in neurodegenerative conditions and the potential of specific NRF2 activators as therapeutic agents.

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Figure 1. Object location memory. CAW treatment (2g/L for 13 months) improved performance in 18-month-old WT but not NRF2KO mice. NRF2KO mice were also impaired relative to age-matched WT animals. n = 4–8, *p< .05, **p < .01. WT = wild-type; NRF2KO = nuclear factor erythroid 2-related factor 2 knockout.CC BY-NC · PubMed Central

Figure 2. Summary of neuroprotective effects of NRF2 activation. NRF2 = nuclear factor erythroid 2-related factor 2; ROS = reactive oxygen species; ARE = antioxidant response element.CC BY-NC · PubMed Central

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Authors: Brandes, M. S., & Gray, N. E.
Affiliations: Oregon Health & Science University (US)
Corresponding author: Gray, Nora E.
ORCID: Brandes, Mikah S.
Gray, Nora E.
Venue: ASN Neuro
Publisher: Informa UK Limited
Published: 2020-01
Volume: 12
Issue: 1
Pages: 1759091419899782-1759091419899782
ISSN: 1759-0914 (ISSN-L)
DOI: 10.1177/1759091419899782
PMC: PMC6977098
OpenAlex: W3002509135
Cited by: 297
References: 313
Citations by year: 2026: 45 · 2025: 52 · 2024: 40 · 2023: 42 · 2022: 43 · 2021: 57 · 2020: 18
FWCI: 3.85
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/4.0/ (vor)
Locations: ASN NEURO (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute of General Medical Sciences (UL1GM118964, TL4GM118965, RL5GM118963)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords: Nrf2, neurodegenerative diseases, oxidative stress, reactive oxygen species, Nrf2 activators, neuroinflammation, mitochondrial dysfunction, mitochondrial biogenesis, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, stroke
MeSH terms: Animals, Anti-Inflammatory Agents, Antioxidants, Humans, Drug Delivery Systems, Reactive Oxygen Species, Oxidative Stress, Neurodegenerative Diseases, NF-E2-Related Factor 2

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NRF2 as a Therapeutic Target in Neurodegenerative Diseases

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