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Recent Patents on CNS Drug Discovery
ISSN (Print): 1574-8898
ISSN (Online): 2212-3954
VOLUME: 7
ISSUE: 3
DOI: 10.2174/157488912803252023      Price:  $100









The Nrf2-ARE Pathway: A Valuable Therapeutic Target for the Treatment of Neurodegenerative Diseases

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Author(s): Gururaj Joshi and Jeffrey A. Johnson
Pages 218-229 (12)
Abstract:
Modulation of NF-E2 related factor 2 (Nrf2) has been shown in several neurodegenerative disorders. The overexpression of Nrf2 has become a potential therapeutic avenue for various neurodegenerative disorders such as Parkinson, Amyotrophic lateral sclerosis, and Alzheimer’s disease. The expression of phase II detoxification enzymes is governed by the cis-acting regulatory element known as antioxidant response element (ARE). The transcription factor Nrf2 binds to ARE thereby transcribing multitude of antioxidant genes. Keap1, a culin 3-based E3 ligase that targets Nrf2 for degradation, sequesters Nrf2 in cytoplasm. Disruption of Keap1-Nrf2 interaction or genetic overexpression of Nrf2 can increase the endogenous antioxidant capacity of the brain thereby rendering protection against oxidative stress in neurodegenerative disorders. This review primarily focuses on recent patents that target Nrf2 overexpression as a promising therapeutic strategy for the treatment of neurodegenerative disorders.
Keywords:
Antioxidant response element (ARE), keap1, Nrf2, neurodegenerative disorders, oxidative stress, Parkinson Disease, Amyotrophic Lateral Sclerosis, hepatoma cells, Oxidative stress, Blood radicals
Affiliation:
School of Pharmacy, 6125 Rennebohm Hall, 777 Highland Avenue, University of Wisconsin, Madison, WI 53705, USA.