Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase
Glutathione is an important antioxidant that plays a crucial role in the cellular protection against oxidative stress and detoxification of electrophilic mutagens, and carcinogens. Glutathione transferases are enzymes catalyzing glutathione-dependent reactions that lead to inactivation and conjugati...
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MDPI AG
2022-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/2/296 |
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| author | Juan Segura-Aguilar Patricia Muñoz Jose Inzunza Mukesh Varshney Ivan Nalvarte Bengt Mannervik |
| author_facet | Juan Segura-Aguilar Patricia Muñoz Jose Inzunza Mukesh Varshney Ivan Nalvarte Bengt Mannervik |
| author_sort | Juan Segura-Aguilar |
| collection | DOAJ |
| description | Glutathione is an important antioxidant that plays a crucial role in the cellular protection against oxidative stress and detoxification of electrophilic mutagens, and carcinogens. Glutathione transferases are enzymes catalyzing glutathione-dependent reactions that lead to inactivation and conjugation of toxic compounds, processes followed by subsequent excretion of the detoxified products. Degeneration and loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal neurons generally involves oxidative stress, neuroinflammation, alpha-synuclein aggregation to neurotoxic oligomers, mitochondrial dysfunction, protein degradation dysfunction, and endoplasmic reticulum stress. However, it is still unclear what triggers these neurodegenerative processes. It has been reported that aminochrome may elicit all of these mechanisms and, interestingly, aminochrome is formed inside neuromelanin-containing dopaminergic neurons during neuromelanin synthesis. Aminochrome is a neurotoxic ortho-quinone formed in neuromelanin synthesis. However, it seems paradoxical that the neurotoxin aminochrome is generated during neuromelanin synthesis, even though healthy seniors have these neurons intact when they die. The explanation of this paradox is the existence of protective tools against aminochrome neurotoxicity composed of the enzymes DT-diaphorase, expressed in these neurons, and glutathione transferase M2-2, expressed in astrocytes. Recently, it has been reported that dopaminergic neurons can be protected by glutathione transferase M2-2 from astrocytes, which secrete exosomes containing the protective enzyme. |
| first_indexed | 2024-03-09T22:45:04Z |
| format | Article |
| id | doaj.art-fd770e1abf2f4107ab85dfd93a25cd9b |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T22:45:04Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj.art-fd770e1abf2f4107ab85dfd93a25cd9b2023-11-23T18:31:32ZengMDPI AGAntioxidants2076-39212022-01-0111229610.3390/antiox11020296Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-DiaphoraseJuan Segura-Aguilar0Patricia Muñoz1Jose Inzunza2Mukesh Varshney3Ivan Nalvarte4Bengt Mannervik5Molecular and Clinical Pharmacology ICBM, Faculty of Medicine, University of Chile, Santiago 8380000, ChileInstituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8900000, ChileDepartment of Biosciences and Nutrition, Karolinska Institutet, SE-14157 Huddinge, SwedenDepartment of Biosciences and Nutrition, Karolinska Institutet, SE-14157 Huddinge, SwedenDepartment of Biosciences and Nutrition, Karolinska Institutet, SE-14157 Huddinge, SwedenDepartment of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-10691 Stockholm, SwedenGlutathione is an important antioxidant that plays a crucial role in the cellular protection against oxidative stress and detoxification of electrophilic mutagens, and carcinogens. Glutathione transferases are enzymes catalyzing glutathione-dependent reactions that lead to inactivation and conjugation of toxic compounds, processes followed by subsequent excretion of the detoxified products. Degeneration and loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal neurons generally involves oxidative stress, neuroinflammation, alpha-synuclein aggregation to neurotoxic oligomers, mitochondrial dysfunction, protein degradation dysfunction, and endoplasmic reticulum stress. However, it is still unclear what triggers these neurodegenerative processes. It has been reported that aminochrome may elicit all of these mechanisms and, interestingly, aminochrome is formed inside neuromelanin-containing dopaminergic neurons during neuromelanin synthesis. Aminochrome is a neurotoxic ortho-quinone formed in neuromelanin synthesis. However, it seems paradoxical that the neurotoxin aminochrome is generated during neuromelanin synthesis, even though healthy seniors have these neurons intact when they die. The explanation of this paradox is the existence of protective tools against aminochrome neurotoxicity composed of the enzymes DT-diaphorase, expressed in these neurons, and glutathione transferase M2-2, expressed in astrocytes. Recently, it has been reported that dopaminergic neurons can be protected by glutathione transferase M2-2 from astrocytes, which secrete exosomes containing the protective enzyme.https://www.mdpi.com/2076-3921/11/2/296glutathioneglutathione transferasedopamineParkinson’s diseaseneuronastrocytes |
| spellingShingle | Juan Segura-Aguilar Patricia Muñoz Jose Inzunza Mukesh Varshney Ivan Nalvarte Bengt Mannervik Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase Antioxidants glutathione glutathione transferase dopamine Parkinson’s disease neuron astrocytes |
| title | Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase |
| title_full | Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase |
| title_fullStr | Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase |
| title_full_unstemmed | Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase |
| title_short | Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase |
| title_sort | neuroprotection against aminochrome neurotoxicity glutathione transferase m2 2 and dt diaphorase |
| topic | glutathione glutathione transferase dopamine Parkinson’s disease neuron astrocytes |
| url | https://www.mdpi.com/2076-3921/11/2/296 |
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