Neurons have long axons and dendrites and most of the proteins needed are synthesized on axonal ribosomes. This requires RNA transport from cell soma to axons and foresees that mechanisms regulating mRNA transport and stability play crucial roles in neuronal function. We discovered that mRNA methylation at adenosine position N6 (m6A) is a novel pathway responsible for neuronal survival. We found small molecules that regulate mRNA m6A, protect and regenerate human DA neurons in vitro and mouse neurons in animal model of Parkinson's disease (PD). We plan to investigate mechanisms of m6A-mediated neuronal survival and clarify the cross-talk with neurotrophic factors in this process. We aim to identify death pathways activated in neurons, which are dying due to the m6A pathway inhibition. Using two animal models of PD we will evaluate the effects of our novel m6A activator on the motor and non-motor symptoms of PD and potentially find a disease-modifying therapy for PD.

2025

2029