RAS and downstream RAF-MEK and PI3K-AKT signaling in neuronal development, function and dysfunction

In postmitotic neurons, the activation of RAS family small GTPases regulates survival, growth and differentiation. Dysregulation of RAS or its major effector pathway, the cascade of RAF-, mitogen-activated and extracellular-signal regulated kinase kinases (MEK), and extracellular-signal regulated kinases (ERK) causes the RASopathies, a group of neurodevelopmental disorders whose pathogenic mechanisms are the subject of intense research. I here summarize the functions of RAS-RAF-MEK-ERK signaling in neurons in vivo, and discuss perspectives for harnessing this pathway to enable novel treatments for nervous system injury, the RASopathies, and possibly other neurological conditions.