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The Ras-ERK signalling pathway in striatum-dependent plasticity and diseases

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Hyperdopaminergic disorders include addictive behaviour in response to psychostimulants and L-dopa induced dyskinesia in Parkinsons’s Disease patients. They are characterised by abnormal cellular changes in the basal ganglia system and in particular in the striatum. Among the intracellular signalling cascades that are found altered in these two brain diseases, the Ras-ERK pathway seems to play a key role in the pathogenesis. Here it will be demonstrated that Ras-GRF1, as a striatal integrator of dopamine and glutamate signals to Ras and ERK , is not only essential for generating the abnormal behavioural responses to cocaine but also for producing motor symptoms associated to chronic L-dopa treatment in animal model of Parkinson’s Disease. Experimental evidence supporting a therapeutic approach for these brain diseases based on Ras-ERK inhibition will also be provided.

This talk is part of the BRC Seminar Series series.

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