The development of orally bioavailable, brain-penetrant, CNS-active p38α MAPK inhibitors provides not only a valuable research tool for testing hypotheses about the role of p38α MAPK in CNS disorders, but also represents a foundation for future drug discovery efforts to develop potential neurodegenerative disease-modifying therapeutics that target this critical gene-regulating protein kinase. Here, WEE1 is linked to neurodegenerative disease.