Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription.
The NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway regulates phase 2 detoxification genes, including a variety of antioxidative enzymes. We tested neuroprotective effects of the synthetic triterpenoid CDDO-MA, a potent activator of the Nrf2/ARE signaling. CDDO-MA...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-06-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2684590?pdf=render |
| _version_ | 1811205958738640896 |
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| author | Lichuan Yang Noel Y Calingasan Bobby Thomas Rajnish K Chaturvedi Mahmoud Kiaei Elizabeth J Wille Karen T Liby Charlotte Williams Darlene Royce Renee Risingsong Eric S Musiek Jason D Morrow Michael Sporn M Flint Beal |
| author_facet | Lichuan Yang Noel Y Calingasan Bobby Thomas Rajnish K Chaturvedi Mahmoud Kiaei Elizabeth J Wille Karen T Liby Charlotte Williams Darlene Royce Renee Risingsong Eric S Musiek Jason D Morrow Michael Sporn M Flint Beal |
| author_sort | Lichuan Yang |
| collection | DOAJ |
| description | The NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway regulates phase 2 detoxification genes, including a variety of antioxidative enzymes. We tested neuroprotective effects of the synthetic triterpenoid CDDO-MA, a potent activator of the Nrf2/ARE signaling. CDDO-MA treatment of neuroblastoma SH-SY5Y cells resulted in Nrf2 upregulation and translocation from cytosol to nucleus and subsequent activation of ARE pathway genes. CDDO-MA blocked t-butylhydroperoxide-induced production of reactive oxygen species (ROS) by activation of ARE genes only in wild type, but not Nrf2 knockout mouse embryonic fibroblasts. Oral administration of CDDO-MA resulted in significant protection against MPTP-induced nigrostriatal dopaminergic neurodegeneration, pathological alpha-synuclein accumulation and oxidative damage in mice. Additionally, CDDO-MA treatment in rats produced significant rescue against striatal lesions caused by the neurotoxin 3-NP, and associated increases in the oxidative damage markers malondialdehyde, F(2)-Isoprostanes, 8-hydroxy-2-deoxyguanosine, 3-nitrotyrosine, and impaired glutathione homeostasis. Our results indicate that the CDDO-MA renders its neuroprotective effects through its potent activation of the Nrf2/ARE pathway, and suggest that triterpenoids may be beneficial for the treatment of neurodegenerative diseases like Parkinson's disease and Huntington's disease. |
| first_indexed | 2024-04-12T03:39:58Z |
| format | Article |
| id | doaj.art-7b065d494c1646bf872470a869ff8dc8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T03:39:58Z |
| publishDate | 2009-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7b065d494c1646bf872470a869ff8dc82022-12-22T03:49:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-06-0146e575710.1371/journal.pone.0005757Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription.Lichuan YangNoel Y CalingasanBobby ThomasRajnish K ChaturvediMahmoud KiaeiElizabeth J WilleKaren T LibyCharlotte WilliamsDarlene RoyceRenee RisingsongEric S MusiekJason D MorrowMichael SpornM Flint BealThe NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway regulates phase 2 detoxification genes, including a variety of antioxidative enzymes. We tested neuroprotective effects of the synthetic triterpenoid CDDO-MA, a potent activator of the Nrf2/ARE signaling. CDDO-MA treatment of neuroblastoma SH-SY5Y cells resulted in Nrf2 upregulation and translocation from cytosol to nucleus and subsequent activation of ARE pathway genes. CDDO-MA blocked t-butylhydroperoxide-induced production of reactive oxygen species (ROS) by activation of ARE genes only in wild type, but not Nrf2 knockout mouse embryonic fibroblasts. Oral administration of CDDO-MA resulted in significant protection against MPTP-induced nigrostriatal dopaminergic neurodegeneration, pathological alpha-synuclein accumulation and oxidative damage in mice. Additionally, CDDO-MA treatment in rats produced significant rescue against striatal lesions caused by the neurotoxin 3-NP, and associated increases in the oxidative damage markers malondialdehyde, F(2)-Isoprostanes, 8-hydroxy-2-deoxyguanosine, 3-nitrotyrosine, and impaired glutathione homeostasis. Our results indicate that the CDDO-MA renders its neuroprotective effects through its potent activation of the Nrf2/ARE pathway, and suggest that triterpenoids may be beneficial for the treatment of neurodegenerative diseases like Parkinson's disease and Huntington's disease.http://europepmc.org/articles/PMC2684590?pdf=render |
| spellingShingle | Lichuan Yang Noel Y Calingasan Bobby Thomas Rajnish K Chaturvedi Mahmoud Kiaei Elizabeth J Wille Karen T Liby Charlotte Williams Darlene Royce Renee Risingsong Eric S Musiek Jason D Morrow Michael Sporn M Flint Beal Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription. PLoS ONE |
| title | Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription. |
| title_full | Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription. |
| title_fullStr | Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription. |
| title_full_unstemmed | Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription. |
| title_short | Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription. |
| title_sort | neuroprotective effects of the triterpenoid cddo methyl amide a potent inducer of nrf2 mediated transcription |
| url | http://europepmc.org/articles/PMC2684590?pdf=render |
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