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Published on: April 13, 2017
Microglia phagocytic mechanisms: Development informing disease
Rebecca M Beiter1, Patrick W Sheehan1, Dorothy P Schafer1
1Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Abstract:
Microglia are tissue-resident macrophages and professional phagocytes of the central nervous system (CNS). In development, microglia-mediated phagocytosis is important for sculpting the cellular architecture. This includes the engulfment of dead/dying cells, pruning extranumerary synapses and axons, and phagocytosing fragments of myelin sheaths. Intriguingly, these developmental phagocytic mechanisms by which microglia sculpt the CNS are now appreciated as important for eliminating synapses, myelin, and proteins during neurodegeneration. Here, we discuss parallels between neurodevelopment and neurodegeneration, which highlights how development is informing disease. We further discuss recent advances and challenges towards therapeutically targeting these phagocytic pathways and how we can leverage development to overcome these challenges.
Insights
Microglia, the brain's immune cells, use phagocytosis to sculpt the nervous system during development. This same process is crucial for clearing debris in neurodegenerative diseases, offering therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells of the central nervous system (CNS), acting as professional phagocytes.
- During development, microglia-mediated phagocytosis is essential for shaping neural architecture, including synapse and myelin pruning.
- These phagocytic functions are increasingly recognized for their role in clearing cellular debris and pathological proteins during neurodegeneration.
Purpose of the Study:
- To highlight the parallels between microglial functions in neurodevelopment and neurodegeneration.
- To explore how understanding neurodevelopment can inform therapeutic strategies for neurological diseases.
- To discuss current advances and challenges in therapeutically targeting microglial phagocytosis.
Main Methods:
- Comparative analysis of microglial phagocytic roles in distinct physiological and pathological contexts.
- Review of recent scientific literature on neurodevelopment, neurodegeneration, and therapeutic targeting of microglial pathways.
Main Results:
- Significant overlap exists between the phagocytic mechanisms employed by microglia during CNS development and in the context of neurodegeneration.
- Developmental processes provide a framework for understanding and potentially manipulating microglial functions in disease.
- Therapeutic targeting of microglial phagocytosis presents both opportunities and significant challenges.
Conclusions:
- Leveraging insights from neurodevelopment offers a promising avenue for developing novel therapies for neurodegenerative diseases.
- Further research is needed to overcome challenges associated with therapeutically modulating microglial phagocytic pathways.
- Understanding the dual role of microglia in development and disease is key to advancing CNS therapeutics.
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