Oxidative stress has been implicated as a key mechanism underlying neuronal death in Parkinson’s disease. Specific proteins within neurons and neighbouring cells act normally to up-regulate the activity of anti-oxidant genes, which can reduce the impact of oxidative stress, but these proteins can be prevented from translocating into the nuclei of neurons (where their genetic material is stored) by another group of ‘sequestering’ proteins in the cytoplasm. This program is supporting key de-risking steps for the development of small-molecules to disrupt the association between the translocating proteins and their sequestering partners, in order to promote anti-oxidant gene expression. This approach therefore aims to provide long-term protection from neurodegeneration in Parkinson’s. Success on optimisation and in vivo testing will support the case for further funding by UTF to take this program forwards to the clinic.
Small drug molecule targeting Nrf2 in neurodegenerative diseases