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Department of Biological Sciences

The Patel lab published a new study in Biomolecules

Dystonia is a heterogeneous group of movement disorders that causes repetitive and often painful movements of the affected limbs leading to compromised posture and gait patterns. Mutations in the PRKRA gene cause one form of early-onset, progressive generalized dystonia called DYT-PRKRA. The PRKRA gene encodes for PACT protein, which is expressed ubiquitously at varying levels in all examined cell types. One of the well-characterized cellular functions of PACT is to activate the kinase PKR in response to cellular stress. Besides the PKR-regulated cellular stress response pathway, other pathways in which PACT participates include the type I interferon (IFN) induction via cytoplasmic pattern recognition receptors. Pattern recognition receptors recognize, bind to, and are activated by dsRNA, and specialize in the detection of pathogen associated or foreign molecular patterns. While PACT has an important role in regulating the dsRNA-induced IFN production, how dystonia-associated mutations affect this proces remains unknown. In their latest study titled "DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction", co-first authors Dr. Lauren Vaughn (former graduate student now post-doc in the Twiss lab), Kenneth Frederick (graduate student) and Dr. Sam  Burnett (former graduate student now working as a scientist at BioAgilytix) from the Patel lab investigated with their collaborators whether the most prevalent mutation reported in DYT-PRKRA patients alters PACT’s functional role in induction of type I IFNs. They found that this mutation augments PACT’s ability to induce IFN β in response to dsRNA, suggesting a possible involvement of type I IFNs in DYT-PRKRA pathophysiology. A great study!

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