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Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia.
Arterioscler Thromb Vasc Biol. 2021 01; 41(1):97-116.AT

Abstract

Vascular cognitive impairment and dementia (VCID) is an age-related, mild to severe mental disability due to a broad panel of cerebrovascular disorders. Its pathobiology involves neurovascular dysfunction, blood-brain barrier disruption, white matter damage, microRNAs, oxidative stress, neuroinflammation, and gut microbiota alterations, etc. Nrf2 (Nuclear factor erythroid 2-related factor 2) is the master regulator of redox status and controls the transcription of a panel of antioxidative and anti-inflammatory genes. By interacting with NF-κB (nuclear factor-κB), Nrf2 also fine-tunes the cellular oxidative and inflammatory balance. Aging is associated with Nrf2 dysfunction, and increasing evidence has proved the role of Nrf2 in mitigating the VCID process. Based on VCID pathobiologies and Nrf2 studies from VCID and other brain diseases, we point out several hypothetical Nrf2 targets for VCID management, including restoration of endothelial function and neurovascular coupling, preservation of blood-brain barrier integrity, reduction of amyloidopathy, promoting white matter integrity, and mitigating oxidative stress and neuroinflammation. Collectively, the Nrf2 pathway could be a promising direction for future VCID research. Targeting Nrf2 would shed light on VCID managing strategies.

Authors+Show Affiliations

Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, PA.Department of Neurology, Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, PA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

33054394

Citation

Yang, Tuo, and Feng Zhang. "Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 41, no. 1, 2021, pp. 97-116.
Yang T, Zhang F. Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia. Arterioscler Thromb Vasc Biol. 2021;41(1):97-116.
Yang, T., & Zhang, F. (2021). Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia. Arteriosclerosis, Thrombosis, and Vascular Biology, 41(1), 97-116. https://doi.org/10.1161/ATVBAHA.120.314804
Yang T, Zhang F. Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia. Arterioscler Thromb Vasc Biol. 2021;41(1):97-116. PubMed PMID: 33054394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia. AU - Yang,Tuo, AU - Zhang,Feng, Y1 - 2020/10/15/ PY - 2022/01/01/pmc-release PY - 2020/10/16/pubmed PY - 2021/2/2/medline PY - 2020/10/15/entrez KW - blood-brain barrier KW - gut microbiota KW - inflammation KW - neurovascular coupling KW - oxidative stress KW - white matter SP - 97 EP - 116 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 41 IS - 1 N2 - Vascular cognitive impairment and dementia (VCID) is an age-related, mild to severe mental disability due to a broad panel of cerebrovascular disorders. Its pathobiology involves neurovascular dysfunction, blood-brain barrier disruption, white matter damage, microRNAs, oxidative stress, neuroinflammation, and gut microbiota alterations, etc. Nrf2 (Nuclear factor erythroid 2-related factor 2) is the master regulator of redox status and controls the transcription of a panel of antioxidative and anti-inflammatory genes. By interacting with NF-κB (nuclear factor-κB), Nrf2 also fine-tunes the cellular oxidative and inflammatory balance. Aging is associated with Nrf2 dysfunction, and increasing evidence has proved the role of Nrf2 in mitigating the VCID process. Based on VCID pathobiologies and Nrf2 studies from VCID and other brain diseases, we point out several hypothetical Nrf2 targets for VCID management, including restoration of endothelial function and neurovascular coupling, preservation of blood-brain barrier integrity, reduction of amyloidopathy, promoting white matter integrity, and mitigating oxidative stress and neuroinflammation. Collectively, the Nrf2 pathway could be a promising direction for future VCID research. Targeting Nrf2 would shed light on VCID managing strategies. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/33054394/Targeting_Transcription_Factor_Nrf2__Nuclear_Factor_Erythroid_2_Related_Factor_2__for_the_Intervention_of_Vascular_Cognitive_Impairment_and_Dementia_ L2 - https://www.ahajournals.org/doi/10.1161/ATVBAHA.120.314804?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -