{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:31:40Z","timestamp":1779100300390,"version":"3.51.4"},"reference-count":175,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T00:00:00Z","timestamp":1562889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["2R01-DA029121"],"award-info":[{"award-number":["2R01-DA029121"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cellular defense mechanisms, intracellular signaling, and physiological functions are regulated by electrophiles and reactive oxygen species (ROS). Recent works strongly considered imbalanced ROS and electrophile overabundance as the leading cause of cellular and tissue damage, whereas oxidative stress (OS) plays a crucial role for the onset and progression of major cerebrovascular and neurodegenerative pathologies. These include Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington\u2019s disease (HD), stroke, and aging. Nuclear factor erythroid 2-related factor (NRF2) is the major modulator of the xenobiotic-activated receptor (XAR) and is accountable for activating the antioxidative response elements (ARE)-pathway modulating the detoxification and antioxidative responses of the cells. NRF2 activity, however, is also implicated in carcinogenesis protection, stem cells regulation, anti-inflammation, anti-aging, and so forth. Herein, we briefly describe the NRF2\u2013ARE pathway and provide a review analysis of its functioning and system integration as well as its role in major CNS disorders. We also discuss NRF2-based therapeutic approaches for the treatment of neurodegenerative and cerebrovascular disorders.<\/jats:p>","DOI":"10.3390\/ijms20143433","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T11:49:38Z","timestamp":1562932178000},"page":"3433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Cerebrovascular and Neurological Disorders: Protective Role of NRF2"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-3712","authenticated-orcid":false,"given":"Farzane","family":"Sivandzade","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditya","family":"Bhalerao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-7162","authenticated-orcid":false,"given":"Luca","family":"Cucullo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"},{"name":"Center for Blood Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.jnutbio.2015.08.001","article-title":"The complexity of the Nrf2 pathway: beyond the antioxidant response","volume":"26","author":"Huang","year":"2015","journal-title":"J. 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