Methods and compositions are provided for preventing or treating neurodegenerative disease and other related diseases and disorders in a mammalian subject. The method provides administering to the mammalian subject a compound capable of inhibiting a PGE2 receptor, e.g., subtype EP2, wherein the compound is administered in an amount effective to treat the neurodegenerative disease or to prevent its occurrence or recurrence. A method for identifying compounds capable of inhibiting neurodegenerative disease is also provided.