Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease
Oxidative stress and neuroinflammation are common bases for disease onset and progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting in dopamine depletion, the pathogenesis differs between hereditary and soli...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/1/170 |
| _version_ | 1797496199540899840 |
|---|---|
| author | Shinichi Takahashi Kyoko Mashima |
| author_facet | Shinichi Takahashi Kyoko Mashima |
| author_sort | Shinichi Takahashi |
| collection | DOAJ |
| description | Oxidative stress and neuroinflammation are common bases for disease onset and progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting in dopamine depletion, the pathogenesis differs between hereditary and solitary disease forms and is often unclear. In addition to the pathogenicity of alpha-synuclein as a pathological disease marker, the involvement of dopamine itself and its interactions with glial cells (astrocyte or microglia) have attracted attention. Pacemaking activity, which is a hallmark of dopaminergic neurons, is essential for the homeostatic maintenance of adequate dopamine concentrations in the synaptic cleft, but it imposes a burden on mitochondrial oxidative glucose metabolism, leading to reactive oxygen species production. Astrocytes provide endogenous neuroprotection to the brain by producing and releasing antioxidants in response to oxidative stress. Additionally, the protective function of astrocytes can be modified by microglia. Some types of microglia themselves are thought to exacerbate Parkinson disease by releasing pro-inflammatory factors (M1 microglia). Although these inflammatory microglia may further trigger the inflammatory conversion of astrocytes, microglia may induce astrocytic neuroprotective effects (A2 astrocytes) simultaneously. Interestingly, both astrocytes and microglia express dopamine receptors, which are upregulated in the presence of neuroinflammation. The anti-inflammatory effects of dopamine receptor stimulation are also attracting attention because the functions of astrocytes and microglia are greatly affected by both dopamine depletion and therapeutic dopamine replacement in Parkinson disease. In this review article, we will focus on the antioxidative and anti-inflammatory effects of astrocytes and their synergism with microglia and dopamine. |
| first_indexed | 2024-03-10T03:00:16Z |
| format | Article |
| id | doaj.art-e2fef5dc3ed54bcaa70bffdc42e7674e |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T03:00:16Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e2fef5dc3ed54bcaa70bffdc42e7674e2023-11-23T12:48:28ZengMDPI AGAntioxidants2076-39212022-01-0111117010.3390/antiox11010170Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson DiseaseShinichi Takahashi0Kyoko Mashima1Department of Neurology and Stroke, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi 350-1298, JapanDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanOxidative stress and neuroinflammation are common bases for disease onset and progression in many neurodegenerative diseases. In Parkinson disease, which is characterized by the degeneration of dopaminergic neurons resulting in dopamine depletion, the pathogenesis differs between hereditary and solitary disease forms and is often unclear. In addition to the pathogenicity of alpha-synuclein as a pathological disease marker, the involvement of dopamine itself and its interactions with glial cells (astrocyte or microglia) have attracted attention. Pacemaking activity, which is a hallmark of dopaminergic neurons, is essential for the homeostatic maintenance of adequate dopamine concentrations in the synaptic cleft, but it imposes a burden on mitochondrial oxidative glucose metabolism, leading to reactive oxygen species production. Astrocytes provide endogenous neuroprotection to the brain by producing and releasing antioxidants in response to oxidative stress. Additionally, the protective function of astrocytes can be modified by microglia. Some types of microglia themselves are thought to exacerbate Parkinson disease by releasing pro-inflammatory factors (M1 microglia). Although these inflammatory microglia may further trigger the inflammatory conversion of astrocytes, microglia may induce astrocytic neuroprotective effects (A2 astrocytes) simultaneously. Interestingly, both astrocytes and microglia express dopamine receptors, which are upregulated in the presence of neuroinflammation. The anti-inflammatory effects of dopamine receptor stimulation are also attracting attention because the functions of astrocytes and microglia are greatly affected by both dopamine depletion and therapeutic dopamine replacement in Parkinson disease. In this review article, we will focus on the antioxidative and anti-inflammatory effects of astrocytes and their synergism with microglia and dopamine.https://www.mdpi.com/2076-3921/11/1/170astrocyteastrogliaglutathionelactatemicrogliaToll-like receptor 4 |
| spellingShingle | Shinichi Takahashi Kyoko Mashima Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease Antioxidants astrocyte astroglia glutathione lactate microglia Toll-like receptor 4 |
| title | Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease |
| title_full | Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease |
| title_fullStr | Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease |
| title_full_unstemmed | Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease |
| title_short | Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease |
| title_sort | neuroprotection and disease modification by astrocytes and microglia in parkinson disease |
| topic | astrocyte astroglia glutathione lactate microglia Toll-like receptor 4 |
| url | https://www.mdpi.com/2076-3921/11/1/170 |
| work_keys_str_mv | AT shinichitakahashi neuroprotectionanddiseasemodificationbyastrocytesandmicrogliainparkinsondisease AT kyokomashima neuroprotectionanddiseasemodificationbyastrocytesandmicrogliainparkinsondisease |