Reduced expression of NUPR1 alleviates epilepsy progression via attenuating ER stress.

Epilepsy is a neurological disorder characterized by recurring seizures. It is necessary to further understand the mechanisms of epilepsy in order to develop novel strategies for its prevention and treatment. Abnormal endoplasmic reticulum stress (ERS) activation is related to the pathogenesis of epilepsy. Nuclear protein 1, transcriptional regulator (NUPR1) is involved in ERS and it might play a role in epilepsy progression. In the present study, we generated an epileptic mouse model using pilocarpine induction. After 72 h of pilocarpine treatment, the expression of NUPR1 was increased in epileptic mice. Furthermore, NUPR1 knockdown reduced the number of spontaneous recurrent seizures and alleviated hippocampal damage in these mice. Interestingly, NUPR1 knockdown also reduced the protein expression levels of LC3, PINK1, and Parkin in the mitochondria, and decreased the PINK1 expression in hippocampus. Additionally, the expression of ERS-related proteins-cleaved caspase-12, ATF4, and CHOP-decreased in epileptic mice following NUPR1 knockdown. In vitro experiments showed that the absence of NUPR1 reduced the expression of ATF4, CHOP, and cleaved caspase-12 in hippocampal neurons and inhibited the neuron apoptosis. In all, our study suggested that NUPR1 maybe a potential molecular target for epilepsy therapy.