title: The Nrf2-ARE pathway: a valuable therapeutic target for the treatment of neurodegenerative diseases.
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.
authors: Division of Pharmaceutical Sciences, School of Pharmacy, 6125 Rennebohm Hall, 777 Highland Avenue, University of Wisconsin, Madison, WI 53705, USA.
authors: Gururaj
authors: G
authors: Joshi
authors: Jeffrey A
authors: JA
authors: Johnson
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D058990:Molecular Targeted Therapy; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D010330:Patents as Topic; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015507:Drugs, Investigational; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents