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Complement dysregulation in the central nervous system during development and disease.

John D Lee1, Liam G Coulthard2, Trent M Woodruff1

  • 1School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Australia.

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|November 12, 2019
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Summary

The complement cascade, crucial for immunity, also regulates brain development and aging. Its proper function is vital for preventing neurodevelopmental and neurodegenerative diseases.

Keywords:
Brain diseaseCentral nervous systemComplementNeurodegenerationNeurodevelopment

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Area of Science:

  • Neuroscience
  • Immunology

Background:

  • The complement cascade is a key immune system component.
  • Complement proteins have critical roles in the developing and aging central nervous system (CNS).
  • These roles extend beyond immunity, influencing neurodevelopment, neurotrauma, and neurodegeneration.

Purpose of the Study:

  • To review the functional roles of complement in brain formation.
  • To examine complement dysregulation in acute and chronic CNS diseases.
  • To present models for complement's involvement in neurodevelopmental and neurodegenerative disorders.

Main Methods:

  • Comprehensive literature review of complement's role in CNS.
  • Analysis of evidence for complement function in brain development.
  • Examination of complement's impact on neurotrauma and neurodegenerative diseases.

Main Results:

  • Complement signaling is integral to neurodevelopmental processes like neural tube closure and synaptic pruning.
  • Complement contributes to both damage and repair following acute CNS injury.
  • Chronic complement activation is linked to neuronal loss and glial activation in aging CNS diseases.

Conclusions:

  • Appropriate complement regulation is essential for healthy CNS development and function.
  • Dysregulated complement activity can lead to neurodevelopmental disorders (e.g., schizophrenia, autism).
  • Complement can either protect against or exacerbate neurodegenerative diseases (e.g., Alzheimer's, ALS).