Work

Molecular mechanisms in DYT-PRKRA: pathways regulated by PKR activator protein PACT

Year: 2025

Type: article

Abstract: Dystonia-PRKRA (DYT-PRKRA), previously termed dystonia 16 (DYT16), is a movement disorder which currently has very limited treatments available and no cure. To develop effective therapeutic options, it is essential to characterize the underlying pathophysiology and identify potential drug targets. This review summarizes the recent studies that shed light on the molecular mechanisms involved in DYT-PRKRA pathogenesis. PRKRA gene encodes for the protein PACT (Protein Activator of the Protein Kinase R) and individuals with DYT-PRKRA mutations develop early-onset generalized dystonia. While the precise mechanisms linking PRKRA mutations to neuronal etiology of dystonia remain incompletely understood, recent research indicates that such mutations cause dysregulation of signaling pathways involved in cellular stress response as well as in production of antiviral cytokines interferons (IFNs). This review focuses on the effect of DYT-PRKRA mutations on the known cellular functions of PACT.

Source: Dystonia

DOI: 10.3389/dyst.2025.14224

Authors: Tricia A. Simon, Rekha C. Patel

Institution: University of South Carolina

Language: English

Topic: Neurological disorders and treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,500