Nrf2—a therapeutic target for the treatment of neurodegenerative diseases |
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| Institution: | 1. King’s College London, UK;2. University of California-Merced, USA;3. Tohoku University, Japan;4. University of Pittsburgh, USA;5. University of Dundee, UK;1. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA;2. State Key Laboratory of Natural and Biomimetic Drugs, and Peking University School of Pharmaceutical Sciences, Beijing 100191, PR China;1. Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK;2. AstraZeneca Oncology Innovative Medicines, Bioscience, 33F197 Mereside, Alderley Park, Cheshire SK10 4TG, UK;3. Center of Excellence in Environmental Toxicology, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6160, USA;1. Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu 501-1196, Japan;2. Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan;3. Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi City, Gunma 371-8511, Japan;1. Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology;2. Division of Molecular & Computational Biology, Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, The University of Southern California, Los Angeles, CA 90089-0191, USA;3. School of Natural Science, University of California at Merced, Merced, CA 95344, USA |
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| Abstract: | The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of increased oxidative stress, protein and DNA modification, inflammation, and dysfunctional proteostasis have all been implicated in contributing to the progression of neurodegeneration. The ability of the cell to combat OS/NS and maintain a clearance mechanism for misfolded aggregating proteins determines whether or not it will survive. A critical pathway in this regard is the Nrf2 (nuclear factor erythroid 2-related factor 2)- antioxidant response element (ARE) pathway. Nrf2 activation has been shown to mitigate a number of pathologic mechanisms associated with Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. This review will focus on the role of Nrf2 in these diseases and the potential for Nrf2 activation to attenuate disease progression. |
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| Keywords: | Nrf2 Oxidative stress Alzheimer’s disease Parkinson’s disease Amyotrophic lateral sclerosis Huntington’s disease Multiple sclerosis |
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