Journal
WIRES MECHANISMS OF DISEASE
Volume 14, Issue 3, Pages -Publisher
WILEY
DOI: 10.1002/wsbm.1545
Keywords
brain development; complement system; microglia; synapse elimination; synaptic pruning
Categories
Funding
- National Institute of Neurological Disorders and Stroke [R01NS112389]
- William and Ella Owens Medical Research Foundation
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Synapse elimination, a critical step in neural circuit maturation during brain development, is regulated by the complement-microglia system through diverse molecular signals. Dysregulation of this system may underlie specific circuit defects in developmental brain disorders, implicating it as a potential therapeutic target.
Synapse elimination, also known as synaptic pruning, is a critical step in the maturation of neural circuits during brain development. Mounting evidence indicates that the complement cascade of the innate immune system plays an important role in synapse elimination. Studies indicate that excess synapses during development are opsonized by complement proteins and subsequently phagocytosed by microglia which expresses complement receptors. The process is regulated by diverse molecular signals, including complement inhibitors that affect the activation of complement, as well as signals that affect microglial recruitment and activation. These signals may promote or inhibit the removal of specific sets of synapses during development. The complement-microglia system has also been implicated in the pathogenesis of several developmental brain disorders, suggesting that the dysregulation of mechanisms of synapse pruning may underlie the specific circuitry defects in these diseases. Here, we review the latest evidence on the molecular and cellular mechanisms of complement-dependent and microglia-dependent synapse elimination during brain development, and highlight the potential of this system as a therapeutic target for developmental brain disorders. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Stem Cells and Development Immune System Diseases > Molecular and Cellular Physiology
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