Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease
Parkinson’s disease (PD) is characterized by motor symptoms based on a loss of nigrostriatal dopaminergic neurons and by non-motor symptoms which precede motor symptoms. Neurodegeneration accompanied by an accumulation of α-synuclein is thought to propagate from the enteric nervous system to the cen...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/4/894 |
| _version_ | 1797606660272816128 |
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| author | Ikuko Miyazaki Masato Asanuma |
| author_facet | Ikuko Miyazaki Masato Asanuma |
| author_sort | Ikuko Miyazaki |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is characterized by motor symptoms based on a loss of nigrostriatal dopaminergic neurons and by non-motor symptoms which precede motor symptoms. Neurodegeneration accompanied by an accumulation of α-synuclein is thought to propagate from the enteric nervous system to the central nervous system. The pathogenesis in sporadic PD remains unknown. However, many reports indicate various etiological factors, such as oxidative stress, inflammation, α-synuclein toxicity and mitochondrial impairment, drive neurodegeneration. Exposure to heavy metals contributes to these etiopathogenesis and increases the risk of developing PD. Metallothioneins (MTs) are cysteine-rich metal-binding proteins; MTs chelate metals and inhibit metal-induced oxidative stress, inflammation and mitochondrial dysfunction. In addition, MTs possess antioxidative properties by scavenging free radicals and exert anti-inflammatory effects by suppression of microglial activation. Furthermore, MTs recently received attention as a potential target for attenuating metal-induced α-synuclein aggregation. In this article, we summarize MTs expression in the central and enteric nervous system, and review protective functions of MTs against etiopathogenesis in PD. We also discuss neuroprotective strategies for the prevention of central dopaminergic and enteric neurodegeneration by targeting MTs. This review highlights multifunctional MTs as a target for the development of disease-modifying drugs for PD. |
| first_indexed | 2024-03-11T05:18:17Z |
| format | Article |
| id | doaj.art-b57b552da9e94758958b396c44500a58 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T05:18:17Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b57b552da9e94758958b396c44500a582023-11-17T18:05:52ZengMDPI AGAntioxidants2076-39212023-04-0112489410.3390/antiox12040894Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s DiseaseIkuko Miyazaki0Masato Asanuma1Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanParkinson’s disease (PD) is characterized by motor symptoms based on a loss of nigrostriatal dopaminergic neurons and by non-motor symptoms which precede motor symptoms. Neurodegeneration accompanied by an accumulation of α-synuclein is thought to propagate from the enteric nervous system to the central nervous system. The pathogenesis in sporadic PD remains unknown. However, many reports indicate various etiological factors, such as oxidative stress, inflammation, α-synuclein toxicity and mitochondrial impairment, drive neurodegeneration. Exposure to heavy metals contributes to these etiopathogenesis and increases the risk of developing PD. Metallothioneins (MTs) are cysteine-rich metal-binding proteins; MTs chelate metals and inhibit metal-induced oxidative stress, inflammation and mitochondrial dysfunction. In addition, MTs possess antioxidative properties by scavenging free radicals and exert anti-inflammatory effects by suppression of microglial activation. Furthermore, MTs recently received attention as a potential target for attenuating metal-induced α-synuclein aggregation. In this article, we summarize MTs expression in the central and enteric nervous system, and review protective functions of MTs against etiopathogenesis in PD. We also discuss neuroprotective strategies for the prevention of central dopaminergic and enteric neurodegeneration by targeting MTs. This review highlights multifunctional MTs as a target for the development of disease-modifying drugs for PD.https://www.mdpi.com/2076-3921/12/4/894metallothioneinParkinson’s diseaseneuroprotectionantioxidantmetalsynuclein |
| spellingShingle | Ikuko Miyazaki Masato Asanuma Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease Antioxidants metallothionein Parkinson’s disease neuroprotection antioxidant metal synuclein |
| title | Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease |
| title_full | Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease |
| title_fullStr | Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease |
| title_full_unstemmed | Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease |
| title_short | Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson’s Disease |
| title_sort | multifunctional metallothioneins as a target for neuroprotection in parkinson s disease |
| topic | metallothionein Parkinson’s disease neuroprotection antioxidant metal synuclein |
| url | https://www.mdpi.com/2076-3921/12/4/894 |
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