Interferon-inducible double-stranded RNA-dependent protein kinase activator A

PRKRA (Interferon-inducible double-stranded RNA-dependent protein kinase activator A) is a 313-amino acid protein that activates the kinase EIF2AK2/PKR, leading to phosphorylation of translation initiation factors and apoptosis induction (UniProt: O75569). It plays roles in siRNA-mediated gene silencing and p53 regulation. The protein is primarily known from studies of early-onset dystonia-parkinsonism (Dystonia 16), where loss-of-function mutations impair its function.

In Alzheimer's Disease, PRKRA is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is +0.64 across examined subcellular fractions, indicating increased abundance in AD brain samples. This elevation may reflect activation of stress-response pathways, including translational control and apoptosis, commonly dysregulated in neurodegeneration.