Microglial dynamics and neuroinflammation in prodromal and early Parkinson’s disease
Abstract Parkinson’s disease (PD) is characterized by a drastic loss of dopaminergic neurons already at diagnosis. As this loss of neurons starts decades before diagnosis, understanding the prodromal stages of the disease might offer novel strategies to curb its progression. While the precise pathog...
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| Format: | Article |
| Language: | English |
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BMC
2025-05-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03462-y |
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| author | Frida Lind-Holm Mogensen Philip Seibler Anne Grünewald Alessandro Michelucci |
| author_facet | Frida Lind-Holm Mogensen Philip Seibler Anne Grünewald Alessandro Michelucci |
| author_sort | Frida Lind-Holm Mogensen |
| collection | DOAJ |
| description | Abstract Parkinson’s disease (PD) is characterized by a drastic loss of dopaminergic neurons already at diagnosis. As this loss of neurons starts decades before diagnosis, understanding the prodromal stages of the disease might offer novel strategies to curb its progression. While the precise pathogenic mechanisms underlying PD remain incompletely understood, growing evidence suggests that neuroinflammation and immune dysregulation play a central role in the development and progression of the disease. Here, we delve into the emerging roles of microglia, the resident immune cells of the central nervous system, in the pathogenesis of prodromal and early-stage PD. We emphasize that microglia contribute to neuroinflammation, protein aggregation and neurodegeneration, although the underlying mechanisms are not yet known. Neuroimaging studies have provided valuable insights into the patterns of microglial activation detected in individuals with prodromal PD and at the time of clinical diagnosis. Furthermore, we highlight the complex interplay between immune dysregulation and neurodegeneration along PD development, including alterations in the peripheral immune system, brain-gut interactions and brain-immune interfaces. Lastly, we outline existing models for investigating microglial involvement in prodromal PD, along with the impact of anti-inflammatory therapies and strategies to modify risk factors. In conclusion, targeting microglial activation and immune dysfunctions in individuals at risk of PD could represent a promising preventive measure and may offer novel therapeutic strategies for early intervention and disease modification. |
| format | Article |
| id | doaj-art-9cbf6cb695f043debaea82d6ce58dbc2 |
| institution | DOAJ |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-9cbf6cb695f043debaea82d6ce58dbc22025-08-20T03:08:43ZengBMCJournal of Neuroinflammation1742-20942025-05-0122111710.1186/s12974-025-03462-yMicroglial dynamics and neuroinflammation in prodromal and early Parkinson’s diseaseFrida Lind-Holm Mogensen0Philip Seibler1Anne Grünewald2Alessandro Michelucci3Neuro-Immunology Group, Department of Cancer Research, Luxembourg Institute of HealthInstitute of Neurogenetics, University of Lübeck and University Hospital Schleswig-HolsteinLuxembourg Centre for Systems Biomedicine, University of LuxembourgNeuro-Immunology Group, Department of Cancer Research, Luxembourg Institute of HealthAbstract Parkinson’s disease (PD) is characterized by a drastic loss of dopaminergic neurons already at diagnosis. As this loss of neurons starts decades before diagnosis, understanding the prodromal stages of the disease might offer novel strategies to curb its progression. While the precise pathogenic mechanisms underlying PD remain incompletely understood, growing evidence suggests that neuroinflammation and immune dysregulation play a central role in the development and progression of the disease. Here, we delve into the emerging roles of microglia, the resident immune cells of the central nervous system, in the pathogenesis of prodromal and early-stage PD. We emphasize that microglia contribute to neuroinflammation, protein aggregation and neurodegeneration, although the underlying mechanisms are not yet known. Neuroimaging studies have provided valuable insights into the patterns of microglial activation detected in individuals with prodromal PD and at the time of clinical diagnosis. Furthermore, we highlight the complex interplay between immune dysregulation and neurodegeneration along PD development, including alterations in the peripheral immune system, brain-gut interactions and brain-immune interfaces. Lastly, we outline existing models for investigating microglial involvement in prodromal PD, along with the impact of anti-inflammatory therapies and strategies to modify risk factors. In conclusion, targeting microglial activation and immune dysfunctions in individuals at risk of PD could represent a promising preventive measure and may offer novel therapeutic strategies for early intervention and disease modification.https://doi.org/10.1186/s12974-025-03462-yMicrogliaNeuroinflammationParkinson’s diseaseProdromal stageREM-sleep behaviour disorder |
| spellingShingle | Frida Lind-Holm Mogensen Philip Seibler Anne Grünewald Alessandro Michelucci Microglial dynamics and neuroinflammation in prodromal and early Parkinson’s disease Journal of Neuroinflammation Microglia Neuroinflammation Parkinson’s disease Prodromal stage REM-sleep behaviour disorder |
| title | Microglial dynamics and neuroinflammation in prodromal and early Parkinson’s disease |
| title_full | Microglial dynamics and neuroinflammation in prodromal and early Parkinson’s disease |
| title_fullStr | Microglial dynamics and neuroinflammation in prodromal and early Parkinson’s disease |
| title_full_unstemmed | Microglial dynamics and neuroinflammation in prodromal and early Parkinson’s disease |
| title_short | Microglial dynamics and neuroinflammation in prodromal and early Parkinson’s disease |
| title_sort | microglial dynamics and neuroinflammation in prodromal and early parkinson s disease |
| topic | Microglia Neuroinflammation Parkinson’s disease Prodromal stage REM-sleep behaviour disorder |
| url | https://doi.org/10.1186/s12974-025-03462-y |
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