Targeting Ras/ERK signaling in the striatum: will it help?

Research in neuroscience and pharmacology over the last decades has not yet provided us with effective treatments for neuropsychiatric diseases such as Huntington's disease (HD), Alzheimer's disease (AD) or drug addiction. On the other hand, pharmacological targeting of the monoaminergic systems has been proven largely successful in the therapy for Parkinson's disease (PD), schizophrenia, and depression.1,2,3 However, further progress in therapy is hampered by our poor understanding of the cellular effects of the available drugs on neural functions. It is conceivable that while the benefits of long-term systemic treatments are caused by adaptive mechanisms in specific brain areas, at the same time side effects may arise from conflicting synaptic adaptations in the same or other structures. Downstream to neurotransmitters and their receptors, possible cellular candidates implicated in such long-term synaptic changes include signaling components that transduce information to the transcriptional machinery in the cell nucleus, and therefore regulate gene expression. As investigation tool for evaluating whether alterations in these molecular processes within the brain may affect learning processes and behavioral responses in general, the analysis of genetically modified mice has proven to be one of the most successful