Abstract

Motor neuron disease (MND) is a fatal and rapidly progressing disease without effective treatment. The innate complement system is upregulated in MND, with recent studies indicating that the activation products C3a and C5a may play a key role in disease progression via its receptors C3aR, C5aR1 and C5aR2.

This study examined the pathological role of C3aR, C5aR1 and C5aR2 in SOD1G93A mouse model of MND, using a combination of knockout mice, and pharmacological inhibition. The effect of C3aR, C5aR1 and C5aR2 genetic ablation and pharmacological inhibition of C5aR1 using PMX205 on disease progression of SOD1G93A mice was determined using body weight, hind limb grip strength, survival time and molecular analysis of spinal cord, tibialis anterior and blood. The results confirm that C5aR1 and C5aR2 plays a pathogenic role in SOD1G93A mice, while C3aR plays a neuroprotective role in SOD1G93A mice. This suggests that inhibition of C5a signalling while promoting C3a signalling could be potential therapeutic targets to slow disease progression in MND.

Bio

John is an early career researcher and Career Track Fellow of the School of Biomedical Sciences (SBMS) who has training in neuroscience, and additional experience in pharmacology and immunity. He completed his honours and Ph.D. at UQ with A/Prof Peter Noakes and Prof Trent Woodruff. He continued his post-doctoral research studies in the field of neuroinflammation and neurodegenerative diseases with Prof Pamela McCombe at UQCCR after obtaining a MNDRIA postdoctoral fellowship. He is now an Advance Queensland research fellow at SBMS, where he focusses on innate immune and inflammatory pathways including the complement system and inflammasomes in motor neuron disease, Huntington’s disease and COVID-19.

 

About Research Seminar Series

The School of Biomedical Sciences Seminar Series presents seminars by international and national researchers as well as local researchers and postdocs.

Unless otherwise indicated, seminars are held in the QBI Auditorium, Level 7 on Mondays from 1.00-2.00pm.

Venue

Room: 
63-348 and zoom: https://uqz.zoom.us/j/87145315677