Glutathione and Related Molecules in Parkinsonism
Glutathione (GSH) is the most abundant intrinsic antioxidant in the central nervous system, and its substrate cysteine readily becomes the oxidized dimeric cystine. Since neurons lack a cystine transport system, neuronal GSH synthesis depends on cystine uptake via the cystine/glutamate exchange tran...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/16/8689 |
| _version_ | 1797523558129205248 |
|---|---|
| author | Masato Asanuma Ikuko Miyazaki |
| author_facet | Masato Asanuma Ikuko Miyazaki |
| author_sort | Masato Asanuma |
| collection | DOAJ |
| description | Glutathione (GSH) is the most abundant intrinsic antioxidant in the central nervous system, and its substrate cysteine readily becomes the oxidized dimeric cystine. Since neurons lack a cystine transport system, neuronal GSH synthesis depends on cystine uptake via the cystine/glutamate exchange transporter (xCT), GSH synthesis, and release in/from surrounding astrocytes. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), a detoxifying master transcription factor, is expressed mainly in astrocytes and activates the gene expression of various phase II drug-metabolizing enzymes or antioxidants including GSH-related molecules and metallothionein by binding to the antioxidant response element (ARE) of these genes. Accumulating evidence has shown the involvement of dysfunction of antioxidative molecules including GSH and its related molecules in the pathogenesis of Parkinson’s disease (PD) or parkinsonian models. Furthermore, we found several agents targeting GSH synthesis in the astrocytes that protect nigrostriatal dopaminergic neuronal loss in PD models. In this article, the neuroprotective effects of supplementation and enhancement of GSH and its related molecules in PD pathology are reviewed, along with introducing new experimental findings, especially targeting of the xCT-GSH synthetic system and Nrf2–ARE pathway in astrocytes. |
| first_indexed | 2024-03-10T08:44:40Z |
| format | Article |
| id | doaj.art-409baffa23cb4b4b86a0a1d599bb7f6d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:40Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-409baffa23cb4b4b86a0a1d599bb7f6d2023-11-22T07:59:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216868910.3390/ijms22168689Glutathione and Related Molecules in ParkinsonismMasato Asanuma0Ikuko Miyazaki1Department of Medical Neurobiology, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Graduate School of Medical, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanGlutathione (GSH) is the most abundant intrinsic antioxidant in the central nervous system, and its substrate cysteine readily becomes the oxidized dimeric cystine. Since neurons lack a cystine transport system, neuronal GSH synthesis depends on cystine uptake via the cystine/glutamate exchange transporter (xCT), GSH synthesis, and release in/from surrounding astrocytes. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), a detoxifying master transcription factor, is expressed mainly in astrocytes and activates the gene expression of various phase II drug-metabolizing enzymes or antioxidants including GSH-related molecules and metallothionein by binding to the antioxidant response element (ARE) of these genes. Accumulating evidence has shown the involvement of dysfunction of antioxidative molecules including GSH and its related molecules in the pathogenesis of Parkinson’s disease (PD) or parkinsonian models. Furthermore, we found several agents targeting GSH synthesis in the astrocytes that protect nigrostriatal dopaminergic neuronal loss in PD models. In this article, the neuroprotective effects of supplementation and enhancement of GSH and its related molecules in PD pathology are reviewed, along with introducing new experimental findings, especially targeting of the xCT-GSH synthetic system and Nrf2–ARE pathway in astrocytes.https://www.mdpi.com/1422-0067/22/16/8689glutathioneneuroprotectionparkinsonismastrocyteregion specificitystriatum |
| spellingShingle | Masato Asanuma Ikuko Miyazaki Glutathione and Related Molecules in Parkinsonism International Journal of Molecular Sciences glutathione neuroprotection parkinsonism astrocyte region specificity striatum |
| title | Glutathione and Related Molecules in Parkinsonism |
| title_full | Glutathione and Related Molecules in Parkinsonism |
| title_fullStr | Glutathione and Related Molecules in Parkinsonism |
| title_full_unstemmed | Glutathione and Related Molecules in Parkinsonism |
| title_short | Glutathione and Related Molecules in Parkinsonism |
| title_sort | glutathione and related molecules in parkinsonism |
| topic | glutathione neuroprotection parkinsonism astrocyte region specificity striatum |
| url | https://www.mdpi.com/1422-0067/22/16/8689 |
| work_keys_str_mv | AT masatoasanuma glutathioneandrelatedmoleculesinparkinsonism AT ikukomiyazaki glutathioneandrelatedmoleculesinparkinsonism |