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Updated: Aug 25, 2025
Author Spotlight: Insight Into Advances in Prion Diseases Research
Published on: August 11, 2023
Loss of Homeostatic Microglia Signature in Prion Diseases
Yue Wang1, Kristin Hartmann1, Edda Thies1
1Institute of Neuropathology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, Germany.
Abstract:
Prion diseases are neurodegenerative diseases that affect humans and animals. They are always fatal and, to date, no treatment exists. The hallmark of prion disease pathophysiology is the misfolding of an endogenous protein, the cellular prion protein (PrPC), into its disease-associated isoform PrPSc. Besides the aggregation and deposition of misfolded PrPSc, prion diseases are characterized by spongiform lesions and the activation of astrocytes and microglia. Microglia are the innate immune cells of the brain. Activated microglia and astrocytes represent a common pathological feature in neurodegenerative disorders. The role of activated microglia has already been studied in prion disease mouse models; however, it is still not fully clear how they contribute to disease progression. Moreover, the role of microglia in human prion diseases has not been thoroughly investigated thus far, and specific molecular pathways are still undetermined. Here, we review the current knowledge on the different roles of microglia in prion pathophysiology. We discuss microglia markers that are also dysregulated in other neurodegenerative diseases including microglia homeostasis markers. Data on murine and human brain tissues show that microglia are highly dysregulated in prion diseases. We highlight here that the loss of homeostatic markers may especially stand out.
Insights
Microglia, the brain's immune cells, are significantly altered in prion diseases. Understanding their dysregulation, including the loss of homeostatic markers, is crucial for investigating these fatal neurodegenerative conditions.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Prion diseases are fatal, untreatable neurodegenerative disorders caused by misfolded prion proteins (PrPSc).
- Microglia, the brain's innate immune cells, are activated in prion diseases, but their precise role in disease progression remains unclear.
- While studied in mouse models, microglia's role in human prion diseases and their specific molecular pathways are not well understood.
Purpose of the Study:
- To review current knowledge on the diverse roles of microglia in prion pathophysiology.
- To discuss microglia markers, including homeostasis markers, that are also dysregulated in other neurodegenerative diseases.
- To highlight the significant dysregulation of microglia in both murine and human prion diseases.
Main Methods:
- Literature review of current knowledge on microglia in prion pathophysiology.
- Analysis of microglia markers, focusing on those also found in other neurodegenerative diseases.
- Comparison of data from murine and human brain tissues.
Main Results:
- Microglia exhibit significant dysregulation in prion diseases across both murine and human tissues.
- Loss of specific microglia homeostatic markers appears to be a prominent feature.
- Dysregulated microglia markers in prion diseases overlap with those in other neurodegenerative conditions.
Conclusions:
- Microglia play a complex and significant role in prion disease pathophysiology.
- The loss of microglia homeostatic markers is a key finding that warrants further investigation.
- Understanding microglia dysregulation offers potential insights into common pathways across neurodegenerative disorders.
