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

Author(s): Gururaj Joshi, Jeffrey A. Johnson

Journal Name: Recent Patents on CNS Drug Discovery (Discontinued)

Volume 7 , Issue 3 , 2012


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

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Article Details

Year: 2012
Page: [218 - 229]
Pages: 12
DOI: 10.2174/157488912803252023
Price: $65

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