The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease
Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases as strict regulation of integrated mitochondrial functions is essential for neuronal signaling, plasticity, and transmitter release. Many lines of evidence suggest that mitochondrial dysfunction plays a central ro...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.4061/2011/314082 |
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| _version_ | 1832563383238393856 |
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| author | Kemal Ugur Tufekci Ezgi Civi Bayin Sermin Genc Kursad Genc |
| author_facet | Kemal Ugur Tufekci Ezgi Civi Bayin Sermin Genc Kursad Genc |
| author_sort | Kemal Ugur Tufekci |
| collection | DOAJ |
| description | Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases as strict regulation of integrated mitochondrial functions is essential for neuronal signaling, plasticity, and transmitter release. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD). Several PD-associated genes interface with mitochondrial dynamics regulating the structure and function of the mitochondrial network. Mitochondrial dysfunction can induce neuron death through a plethora of mechanisms. Both mitochondrial dysfunction and neuroinflammation, a common denominator of PD, lead to an increased production of reactive oxygen species, which are detrimental to neurons. The transcription factor nuclear factor E2-related factor 2 (Nrf2, NFE2L2) is an emerging target to counteract mitochondrial dysfunction and its consequences in PD. Nrf2 activates the antioxidant response element (ARE) pathway, including a battery of cytoprotective genes such as antioxidants and anti-inflammatory genes and several transcription factors involved in mitochondrial biogenesis. Here, the current knowledge about the role of mitochondrial dysfunction in PD, Nrf2/ARE stress-response mechanisms, and the evidence for specific links between this pathway and PD are summarized. The neuroprotection of nigral dopaminergic neurons by the activation of Nrf2 through several inducers in PD is also emphasized as a promising therapeutic approach. |
| format | Article |
| id | doaj-art-c6cc516e34374aacb9a9429d875f3753 |
| institution | Kabale University |
| issn | 2042-0080 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-c6cc516e34374aacb9a9429d875f37532025-02-03T01:20:26ZengWileyParkinson's Disease2042-00802011-01-01201110.4061/2011/314082314082The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's DiseaseKemal Ugur Tufekci0Ezgi Civi Bayin1Sermin Genc2Kursad Genc3Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Inciralti, 35340 Izmir, TurkeyDepartment of Neuroscience, Health Science Institute, Dokuz Eylul University, Inciralti, 35340 Izmir, TurkeyDepartment of Neuroscience, Health Science Institute, Dokuz Eylul University, Inciralti, 35340 Izmir, TurkeyDepartment of Neuroscience, Health Science Institute, Dokuz Eylul University, Inciralti, 35340 Izmir, TurkeyMitochondrial dysfunction is a prominent feature of various neurodegenerative diseases as strict regulation of integrated mitochondrial functions is essential for neuronal signaling, plasticity, and transmitter release. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD). Several PD-associated genes interface with mitochondrial dynamics regulating the structure and function of the mitochondrial network. Mitochondrial dysfunction can induce neuron death through a plethora of mechanisms. Both mitochondrial dysfunction and neuroinflammation, a common denominator of PD, lead to an increased production of reactive oxygen species, which are detrimental to neurons. The transcription factor nuclear factor E2-related factor 2 (Nrf2, NFE2L2) is an emerging target to counteract mitochondrial dysfunction and its consequences in PD. Nrf2 activates the antioxidant response element (ARE) pathway, including a battery of cytoprotective genes such as antioxidants and anti-inflammatory genes and several transcription factors involved in mitochondrial biogenesis. Here, the current knowledge about the role of mitochondrial dysfunction in PD, Nrf2/ARE stress-response mechanisms, and the evidence for specific links between this pathway and PD are summarized. The neuroprotection of nigral dopaminergic neurons by the activation of Nrf2 through several inducers in PD is also emphasized as a promising therapeutic approach.http://dx.doi.org/10.4061/2011/314082 |
| spellingShingle | Kemal Ugur Tufekci Ezgi Civi Bayin Sermin Genc Kursad Genc The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease Parkinson's Disease |
| title | The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease |
| title_full | The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease |
| title_fullStr | The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease |
| title_full_unstemmed | The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease |
| title_short | The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease |
| title_sort | nrf2 are pathway a promising target to counteract mitochondrial dysfunction in parkinson s disease |
| url | http://dx.doi.org/10.4061/2011/314082 |
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