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Related Experiment Video

Updated: Sep 17, 2025

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Genetic susceptibility to cerebral palsy involves complement system-mediated neuronal development and plasticity

Huang Kun1, Qi Zhou1, Hao Wu1

  • 1Department of Neurology, The First People's Hospital of Fuzhou, Fuzhou, Jiangxi, China.

Scientific Reports
|July 2, 2025
PubMed
Summary

Genetic analysis reveals complement system genes, including CX3CL1 and TYRO3, are linked to cerebral palsy (CP) risk. These findings suggest potential therapeutic targets for CP treatment strategies.

Keywords:
Cerebral palsyComplement system in neuronal development and plasticity pathwayMendelian randomizationPharmaceutical targets

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Area of Science:

  • Neuroscience
  • Genetics
  • Immunology

Background:

  • Cerebral palsy (CP) is a neurological disorder with complex causes, often involving prenatal or perinatal brain injury.
  • The precise genetic underpinnings of CP, particularly involving the complement system in neuronal development and plasticity (CSNDP) pathway, remain largely unknown.

Purpose of the Study:

  • To investigate the causal role of genes in the CSNDP pathway in the pathogenesis of cerebral palsy.
  • To identify specific genes within the CSNDP pathway associated with CP susceptibility and explore their therapeutic potential.

Main Methods:

  • Genome-wide Summary-data based MR (SMR) and Mendelian randomization (MR) analyses were performed.
  • Leveraged large-scale GWAS and QTL data to assess associations between CSNDP-related gene expression, DNA methylation, protein abundance, and CP risk.
  • Colocalization and druggability assessments were conducted, alongside phenome-wide association studies.

Main Results:

  • Several genes, notably CX3CL1 and TYRO3, were identified as putatively causal for CP risk, implicating neuroinflammation and synaptic modulation.
  • Strong evidence from colocalization analysis supported shared genetic variants for CX3CL1 and TYRO3 associations with CP.
  • CX3CL1 and TYRO3 were identified as potential therapeutic targets with no significant adverse effects observed in phenome-wide association studies.

Conclusions:

  • This study elucidates molecular mechanisms in CP pathogenesis by highlighting the role of the CSNDP pathway.
  • CX3CL1 and TYRO3 represent promising therapeutic targets for cerebral palsy interventions.
  • Targeted interventions within the CSNDP pathway offer potential new strategies for CP treatment.