Immune responses in the Parkinson's disease brain
Immune changes occur in all neurodegenerative conditions, but there are significant differences between diseases. For Parkinson's disease (PD), the immune system involvement is still being identified with considerable promise for therapeutic targeting. Post-mortem analyses of PD patient brains...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122000924 |
| _version_ | 1818272827453734912 |
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| author | Fiona Weiss Adahir Labrador-Garrido Nicolas Dzamko Glenda Halliday |
| author_facet | Fiona Weiss Adahir Labrador-Garrido Nicolas Dzamko Glenda Halliday |
| author_sort | Fiona Weiss |
| collection | DOAJ |
| description | Immune changes occur in all neurodegenerative conditions, but there are significant differences between diseases. For Parkinson's disease (PD), the immune system involvement is still being identified with considerable promise for therapeutic targeting. Post-mortem analyses of PD patient brains and pre-clinical cell and rodent models of PD identify increased inflammation in the brain and an elevation in central and peripheral pro-inflammatory cytokines. The cells involved include activated microglia surrounding degenerating neurons, currently thought to be neuroprotective in early disease stages but detrimental at later stages. Very different astrocytic reactions are found in the PD brain compared to other neurodegenerative conditions, with a loss of normal astrocyte functions contributing to a neurotoxic or dysfunctional phenotype (rather than classical astrogliosis found in all other neurodegenerative conditions). Astrocytes in PD are also actively involved in clearing α-synuclein away from vulnerable neurons, but the eventual accumulation of α-synuclein in their cytoplasm promotes a pro-inflammatory response and contributes to their dysfunctional phenotype and the spreading of PD pathology. Infiltration of peripheral immune cells also occurs in the PD brain, particularly T cells and monocytes. Both CD4 and CD8 T cells occur in regions of cell loss, with cytotoxic CD8 T cells occurring in the earliest stages and CD4 T helper cells occurring with disease progression. Current evidence points towards infiltrating monocytes as also playing a role in neuron death. Further characterisation of the successive molecular changes in both the resident and peripheral immune cells invading the PD brain will provide targets for disease modification. |
| first_indexed | 2024-12-12T21:48:15Z |
| format | Article |
| id | doaj.art-ab93cc36726b4672b8c81024e0f31ea6 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-12T21:48:15Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ab93cc36726b4672b8c81024e0f31ea62022-12-22T00:10:52ZengElsevierNeurobiology of Disease1095-953X2022-06-01168105700Immune responses in the Parkinson's disease brainFiona Weiss0Adahir Labrador-Garrido1Nicolas Dzamko2Glenda Halliday3University of Sydney, Brain and Mind Centre and Faculty of Medicine and Health, School of Medical Sciences, Camperdown, NSW 2050, AustraliaUniversity of Sydney, Brain and Mind Centre and Faculty of Medicine and Health, School of Medical Sciences, Camperdown, NSW 2050, AustraliaUniversity of Sydney, Brain and Mind Centre and Faculty of Medicine and Health, School of Medical Sciences, Camperdown, NSW 2050, AustraliaCorresponding author.; University of Sydney, Brain and Mind Centre and Faculty of Medicine and Health, School of Medical Sciences, Camperdown, NSW 2050, AustraliaImmune changes occur in all neurodegenerative conditions, but there are significant differences between diseases. For Parkinson's disease (PD), the immune system involvement is still being identified with considerable promise for therapeutic targeting. Post-mortem analyses of PD patient brains and pre-clinical cell and rodent models of PD identify increased inflammation in the brain and an elevation in central and peripheral pro-inflammatory cytokines. The cells involved include activated microglia surrounding degenerating neurons, currently thought to be neuroprotective in early disease stages but detrimental at later stages. Very different astrocytic reactions are found in the PD brain compared to other neurodegenerative conditions, with a loss of normal astrocyte functions contributing to a neurotoxic or dysfunctional phenotype (rather than classical astrogliosis found in all other neurodegenerative conditions). Astrocytes in PD are also actively involved in clearing α-synuclein away from vulnerable neurons, but the eventual accumulation of α-synuclein in their cytoplasm promotes a pro-inflammatory response and contributes to their dysfunctional phenotype and the spreading of PD pathology. Infiltration of peripheral immune cells also occurs in the PD brain, particularly T cells and monocytes. Both CD4 and CD8 T cells occur in regions of cell loss, with cytotoxic CD8 T cells occurring in the earliest stages and CD4 T helper cells occurring with disease progression. Current evidence points towards infiltrating monocytes as also playing a role in neuron death. Further characterisation of the successive molecular changes in both the resident and peripheral immune cells invading the PD brain will provide targets for disease modification.http://www.sciencedirect.com/science/article/pii/S0969996122000924GliaCytokineImmuneInflammationAlpha-synuclein |
| spellingShingle | Fiona Weiss Adahir Labrador-Garrido Nicolas Dzamko Glenda Halliday Immune responses in the Parkinson's disease brain Neurobiology of Disease Glia Cytokine Immune Inflammation Alpha-synuclein |
| title | Immune responses in the Parkinson's disease brain |
| title_full | Immune responses in the Parkinson's disease brain |
| title_fullStr | Immune responses in the Parkinson's disease brain |
| title_full_unstemmed | Immune responses in the Parkinson's disease brain |
| title_short | Immune responses in the Parkinson's disease brain |
| title_sort | immune responses in the parkinson s disease brain |
| topic | Glia Cytokine Immune Inflammation Alpha-synuclein |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122000924 |
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