Summary
This project aims to understand the mechanisms by which the complement component C1q contributes to synapse elimination in multiple sclerosis (MS)-related neuroinflammatory disease and to develop a therapeutic strategy targeting complement.
Understanding the mechanisms behind complement mediated synapse elimination in neuroinflammatory disease
US · IL
NIH
grant
awarded
#nih-1F30AI197455-01
What they want
The research will investigate how microglia-derived C1q triggers a pro-inflammatory state in microglia and induces astrocytes to secrete C3, which is necessary for synapse loss. Aim 1 involves using in vivo molecular genetic tools to evaluate C1q's role in regulating neuroinflammation and C3 production. Aim 2 will assess if knocking down C1q and C3 expression with antisense oligonucleotides (ASOs) can rescue synapses and attenuate reactive gliosis and neuroinflammation.
Deliverables
- Advanced understanding of how the complement system influences neuroinflammation and synapse loss
- Evaluation of C1q's role in regulating neuroinflammation and C3 production
- Assessment of ASO efficacy in rescuing synapses and attenuating gliosis/neuroinflammation
Technical requirements
- In vivo molecular genetic tools
- Antisense oligonucleotides (ASOs)
- Microscopy
- Transcriptomics
Key personnel
- Dr. Schafer (Sponsor, expert in microglial complement biology and neuroinflammation)
- Dr. Ram (Co-sponsor, clinician and expert in the complement system)
- Dr. Watts (Collaborator, expert in ASOs)
