NLRP3 inflammasome

David Brough, University of Manchester

This project aims to alter inflammatory processes as a means to reduce neuronal damage and cell death in Alzheimer’s disease. Dr Brough’s team is optimising a novel small molecule inhibitor of the NLRP3 inflammasome, a group of proteins which plays a vital role in controlling inflammation, and test in vivo its potential as new Alzheimer’s disease therapy.

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Cytokine receptor CSF1R

Diego Gomez-Nicola, University of Southampton

Dr Gomez-Nicola is developing and optimising inhibitors of the interaction between CSF1R and IL34, key proteins involved in the proliferation of microglia, In previous mouse studies, blocking CSF1R was found to reduce the inflammatory response to protein aggregates in the brain and so reduce neuronal death and improve symptoms in other neurodegenerative diseases where inflammation plays a key role.
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Fractalkine receptor

Kevin Nash, University of South Florida

This programme is exploring the role of an immune system regulator, fractalkine and its receptor, in neurodegeneration. The team hopes to identify and develop a brain penetrant fractalkine receptor agonist, and demonstrate that such agonists dampen neuroinflammation and as a result reduce neuronal death.

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Marco Baralle, International Centre for Genetic Engineering and Biotechnology

Using a unique cell based TDP-43 aggregation model, Dr Baralle’s team is developing assays and performing high-content screening to find selective and potent compounds that clear TDP-43 aggregates. The team will then explore whether the identified compounds can reduce cell death and improve symptoms in motor neurone disease and frontotemporal dementia.
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Jens Schwamborn, University of Luxembourg

Dr Schwamborn’s group is developing and refining small molecule inhibitors of TRIM32, a neuronal cell fate determinant. By inhibiting TRIM32 the team aims to transiently inhibit stem cell differentiation, which is hypothesised to increase the numbers of available stem cells which in turn can stimulate self-renewal and production of more neurons to replace those lost during degeneration.
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