Abstract
The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor well-known for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 383-400 |
| Number of pages | 18 |
| Journal | Biological Chemistry |
| Volume | 397 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2016 |
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Keywords
- bioenergetics
- GSK-3
- Keap1
- mitochondria
- neurodegeneration
- Nrf2
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Molecular Biology
Cite this
Nrf2 activation in the treatment of neurodegenerative diseases : A focus on its role in mitochondrial bioenergetics and function. / Esteras, Noemí; Dinkova-Kostova, Albena T.; Abramov, Andrey Y.
In: Biological Chemistry, Vol. 397, No. 5, 01.05.2016, p. 383-400.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Nrf2 activation in the treatment of neurodegenerative diseases
T2 - A focus on its role in mitochondrial bioenergetics and function
AU - Esteras, Noemí
AU - Dinkova-Kostova, Albena T.
AU - Abramov, Andrey Y.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor well-known for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor.
AB - The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor well-known for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor.
KW - bioenergetics
KW - GSK-3
KW - Keap1
KW - mitochondria
KW - neurodegeneration
KW - Nrf2
UR - http://www.scopus.com/inward/record.url?scp=84964922374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964922374&partnerID=8YFLogxK
U2 - 10.1515/hsz-2015-0295
DO - 10.1515/hsz-2015-0295
M3 - Review article
C2 - 26812787
AN - SCOPUS:84964922374
VL - 397
SP - 383
EP - 400
JO - Biological Chemistry
JF - Biological Chemistry
SN - 1431-6730
IS - 5
ER -