Provided herein are methods for treating a neurodegenerative disease or disorder, or stroke using a combination of one or more RXR agonist and/or one or more Nurr1 agonist and one or more trophic factor, or pharmaceutically acceptable salts thereof. Additionally, compositions comprising of one or more RXR agonist and/or one or more Nurr1 agonist and one or more trophic factor, or pharmaceutically acceptable salts thereof for treatment of a neurodegenerative disease or disorder, or stroke are provided.