Abstract 1511 Molecular mechanisms in dystonia, a movement disorder caused by mutations in the Prkra gene, reveal overactive integrated stress response (ISR) pathway

DYT-PRKRA (Dystonia-PRKRA aka DYT16) is a rare autosomal recessive movement disorder caused by mutations in the Prkra gene, encoding PACT, a protein activator of the interferon-induced protein kinase (PKR). Our previous research indicated that one such mutation, P222L, causes increased PKR activation and dysregulation of the integrated stress response (ISR). Under cellular stress conditions such as endoplasmic reticulum (ER) stress, PACT activates PKR, leading to eIF2α phosphorylation, a key regulatory event in ISR activation.