Grants awarded

The role of the Wallerian axon-death pathway in neuronal and axonal vulnerability in Parkinson's disease

Grantholder:

Dr Andrea Loreto

University of Cambridge

United Kingdom

The reasons why a specific type of nerve cells, called dopaminergic neurons, are particularly vulnerable in Parkinson’s disease (PD) is unknown. These neurons develop huge projections, called axons, which die early in people with PD. Understanding why this happens will inform the development of effective therapies. 

I aim to identify new molecular players that contribute to the vulnerability of dopaminergic neurons and axons in PD. I will perform mechanistic studies in dopaminergic neurons derived from humans and use models of PD in fish. I will test the role of a preventable axon-death programme called Wallerian degeneration, which offers a way to alleviate PD.

These studies could greatly advance our understanding of mechanisms of nerve cell death in PD. The project also has important clinical implications since the Wallerian pathway can be potently blocked. Our findings are also likely to be relevant to other neurodegenerative conditions.