Perampanel improves cognitive function in epilepsy by targeting AMPA receptor subunit GluR2-mediated endoplasmic reticulum stress and synaptic plasticity

Moreover, KA-induced epilepsy mice showed reduced GluR2 expression, decreased dendritic spine density and expression of synaptic function proteins (SYP and PSD95) as well as elevated ERS-related proteins (GRP78, ATF4, CHOP, IRE1α and ATF6), while PER treatment could reverse such changes. Meanwhile, PER treatment could alleviate KA-induced neurotoxicity and synaptic plasticity deficits in hippocampal neurons. In terms of mechanism, GluR2 silencing reversed the protective effects of PER in KA-stimulated hippocampal neurons, and further inhibiting ERS using 4-PBA could offset the effects of GluR2 silencing.</p> <p>GluR2-mediated ERS may involve the improved effects of Perampanel in cognitive function of epilepsy patients by promoting synaptic plasticity.</p> <p></p><p>Perampanel effectively alleviates epileptic seizure behaviors and improves cognitive function</p><p>Perampanel upregulates the expression of AMPA receptor subunit GluR2, thus reducing Ca²⁺ influx</p><p>GluR2 silencing reverses the therapeutic effects of Perampanel in epilepsy</p><p></p> <p>Perampanel effectively alleviates epileptic seizure behaviors and improves cognitive function</p> <p>Perampanel upregulates the expression of AMPA receptor subunit GluR2, thus reducing Ca²⁺ influx</p> <p>GluR2 silencing reverses the therapeutic effects of Perampanel in epilepsy</p>