Agents and methods of treating a psychiatric stress disorder, Rett syndrome, MeCP2 duplication syndrome or multiple sclerosis are provided. Accordingly there is provided an agent capable of down-regulating activity and/or expression of importin alpha5 for use in the treatment of a medical condition selected from the group consisting of psychiatric stress disorder, Rett syndrome, MeCP2 duplication syndrome and multiple sclerosis. Also provided are methods of identifying an agent that inhibits activity of importin alpha5.