Our results show for the first time that activation of EAAT2 with a novel PAM compound iQ-007, leads to both robust protection against seizures and clear-cut neuroprotective effects in models of neurodegeneration (not disclosed herein). Collectively these observations indicate that EAAT2 PAM compounds may have valuable therapeutic potential in epilepsy, and in a range of neurological disorders characterized by hyperexcitability and neurodegeneration.