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NRF2 as a Therapeutic Target in Neurodegenerative Diseases
Open accessAbstract
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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“Another Nrf2 activating compound is Centella asiatica extracts, which can activate Nrf2 in neuroblastoma cells, isolated primary neurons and in the brains of AD and aging mouse models. This activation improved mitochondrial and cognitive function, and enhanced synaptic density [113,114,115].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [113]
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Research works printed but not linked: 1
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Sorted by citations
Buccellato, F. R., D’Anca, M., Fenoglio, C., Scarpini, E., & Galimberti, D. (2021) · Antioxidants · doi:10.3390/antiox10091353 · Cited by 179
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Metadata
- Authors
- Brandes, M. S., & Gray, N. E.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- 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)
- 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
- 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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