Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders
Inherited metabolic disorders (IMDs) are rare genetic conditions that affect multiple organs, predominantly the central nervous system. Since treatment for a large number of IMDs is limited, there is an urgent need to find novel therapeutical targets. Nuclear factor erythroid-2-related factor 2 (Nrf...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2021.785057/full |
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| author | Bianca Seminotti Mateus Grings Paolo Tucci Guilhian Leipnitz Guilhian Leipnitz Guilhian Leipnitz Luciano Saso |
| author_facet | Bianca Seminotti Mateus Grings Paolo Tucci Guilhian Leipnitz Guilhian Leipnitz Guilhian Leipnitz Luciano Saso |
| author_sort | Bianca Seminotti |
| collection | DOAJ |
| description | Inherited metabolic disorders (IMDs) are rare genetic conditions that affect multiple organs, predominantly the central nervous system. Since treatment for a large number of IMDs is limited, there is an urgent need to find novel therapeutical targets. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor that has a key role in controlling the intracellular redox environment by regulating the expression of antioxidant enzymes and several important genes related to redox homeostasis. Considering that oxidative stress along with antioxidant system alterations is a mechanism involved in the neuropathophysiology of many IMDs, this review focuses on the current knowledge about Nrf2 signaling dysregulation observed in this group of disorders characterized by neurological dysfunction. We review here Nrf2 signaling alterations observed in X-linked adrenoleukodystrophy, glutaric acidemia type I, hyperhomocysteinemia, and Friedreich’s ataxia. Additionally, beneficial effects of different Nrf2 activators are shown, identifying a promising target for treatment of patients with these disorders. We expect that this article stimulates research into the investigation of Nrf2 pathway involvement in IMDs and the use of potential pharmacological modulators of this transcription factor to counteract oxidative stress and exert neuroprotection. |
| first_indexed | 2024-12-17T20:03:59Z |
| format | Article |
| id | doaj.art-35e0b41a75c444569c68f800a18d11db |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-17T20:03:59Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-35e0b41a75c444569c68f800a18d11db2022-12-21T21:34:23ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022021-11-011510.3389/fncel.2021.785057785057Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic DisordersBianca Seminotti0Mateus Grings1Paolo Tucci2Guilhian Leipnitz3Guilhian Leipnitz4Guilhian Leipnitz5Luciano Saso6Postgraduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilPostgraduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilDepartment of Clinical and Experimental Medicine, University of Foggia, Foggia, ItalyPostgraduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilDepartment of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, BrazilPostgraduate Program in Biological Sciences: Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilDepartment of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Rome, ItalyInherited metabolic disorders (IMDs) are rare genetic conditions that affect multiple organs, predominantly the central nervous system. Since treatment for a large number of IMDs is limited, there is an urgent need to find novel therapeutical targets. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor that has a key role in controlling the intracellular redox environment by regulating the expression of antioxidant enzymes and several important genes related to redox homeostasis. Considering that oxidative stress along with antioxidant system alterations is a mechanism involved in the neuropathophysiology of many IMDs, this review focuses on the current knowledge about Nrf2 signaling dysregulation observed in this group of disorders characterized by neurological dysfunction. We review here Nrf2 signaling alterations observed in X-linked adrenoleukodystrophy, glutaric acidemia type I, hyperhomocysteinemia, and Friedreich’s ataxia. Additionally, beneficial effects of different Nrf2 activators are shown, identifying a promising target for treatment of patients with these disorders. We expect that this article stimulates research into the investigation of Nrf2 pathway involvement in IMDs and the use of potential pharmacological modulators of this transcription factor to counteract oxidative stress and exert neuroprotection.https://www.frontiersin.org/articles/10.3389/fncel.2021.785057/fullNrf2 signalingantioxidant defensesinherited metabolic disordersneurometabolismneurodegeneration |
| spellingShingle | Bianca Seminotti Mateus Grings Paolo Tucci Guilhian Leipnitz Guilhian Leipnitz Guilhian Leipnitz Luciano Saso Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders Frontiers in Cellular Neuroscience Nrf2 signaling antioxidant defenses inherited metabolic disorders neurometabolism neurodegeneration |
| title | Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders |
| title_full | Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders |
| title_fullStr | Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders |
| title_full_unstemmed | Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders |
| title_short | Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders |
| title_sort | nuclear factor erythroid 2 related factor 2 signaling in the neuropathophysiology of inherited metabolic disorders |
| topic | Nrf2 signaling antioxidant defenses inherited metabolic disorders neurometabolism neurodegeneration |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2021.785057/full |
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