Dystonia is a diverse group of movement disorders that involve repetitive, often painful movements of affected body parts resulting in abnormal gaits and postures. One form of dystonia, DYT-PRKRA (aka DYT16), is caused by mutations in the PRKRA gene, which encodes the protein PACT. Eleven mutations causing DYT-PRKRA have been identified thus far in the PRKRA gene, four of them being dominantly inherited variants. PACT is an activator of protein kinase PKR in response to a variety of stress signals that might affect a cell. Once activated by PACT, PKR phosphorylates the α subunit of the eukaryotic translation initiation factor 2 (eIF2α), causing a transient attenuation of general protein synthesis that enables the cell to restore homeostasis and recover from stress. Previous work from the Patel lab has established that the PRKRA mutations reported to cause DYT-PRKRA lead to enhanced PACT-PKR interactions causing a dysregulation of stress response and an increased sensitivity of cells to apoptosis. In their new study titled "Luteolin protects DYT-PRKRA cells from apoptosis by suppressing PKR activation", graduate student Ken Frederick and his mentor Dr. Rekha Patel explored the effects of luteolin, a plant flavonoid, that inhibits PACT-PKR interaction. They found that luteolin is markedly effective in disrupting the pathological PACT-PKR interactions to protect DYT-PRKRA cells against apoptosis, suggesting a therapeutic option for using luteolin to treat DYT-PRKRA. Congrats!
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- 2023 News Archive
- Kenneth Frederick and Dr. Rekha Patel published a new study in Frontiers in Pharmacology