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Published on: April 13, 2017
Microglia-centered cellular crosstalk in neurodegeneration
1Department of Medicine, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Abstract:
Neuroinflammation shaped by aberrant cellular interactions represents a hallmark of neurodegenerative diseases of the central nervous system (CNS). Microglia are specialized tissue-resident macrophages that reside in the CNS parenchyma and have emerged as central regulators of this aberrant cellular crosstalk. They integrate local signals and orchestrate the cellular interaction networks that underlie disease progression. Recent advances in single-cell and single-nucleus omics, in combination with spatially resolved approaches, have substantially advanced our understanding of microglial dynamics in neurodegeneration. These technological and conceptual advances have revealed an unexpected diversity of disease-associated microglial states and highlighted microglia as central organizers of multicellular interaction networks within diseased CNS tissue. In this chapter, we discuss how these advances have reshaped our understanding of microglia-centered cellular crosstalk in neurodegeneration. We focus on the diversification of neurodegenerative CNS microglial states, the interaction of microglia with neurons, glial cells, adaptive immune cells, and the vasculature. We further discuss how this framework provides a basis for therapeutic strategies aimed at modulating, replacing, or reprogramming microglia in neurodegenerative disease.
Insights
Neuroinflammation in neurodegenerative diseases involves complex cell interactions. Microglia, the brain's immune cells, orchestrate these interactions, with new research revealing diverse microglial states and their central role in disease progression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation and aberrant cellular interactions are key features of neurodegenerative diseases.
- Microglia, the central nervous system (CNS) resident macrophages, are critical regulators of these cellular crosstalks.
- Understanding microglial roles is essential for deciphering disease mechanisms.
Purpose of the Study:
- To review recent advances in understanding microglial dynamics in neurodegeneration.
- To highlight the diversity of disease-associated microglial states.
- To discuss the implications of these findings for therapeutic strategies.
Main Methods:
- Single-cell and single-nucleus omics technologies.
- Spatially resolved approaches.
- Analysis of microglial interactions with other CNS cells and the vasculature.
Main Results:
- Identification of diverse disease-associated microglial states.
- Revelation of microglia as central organizers of multicellular interaction networks in neurodegeneration.
- Demonstration of microglia's interaction with neurons, glial cells, immune cells, and vasculature.
Conclusions:
- Recent omics and spatial technologies have significantly advanced the understanding of microglial roles in neurodegeneration.
- Microglia exhibit diverse states and actively shape cellular crosstalks in diseased CNS tissue.
- This knowledge provides a foundation for developing novel microglia-targeted therapies for neurodegenerative diseases.
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