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

Tricia A. Simon,

Rekha C. Patel

Dystonia, Journal Year: 2025, Volume and Issue: 4

Published: March 13, 2025

Dystonia- PRKRA (DYT- ), 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 essential to characterize the underlying pathophysiology identify potential drug targets. This review summarizes recent studies that shed light on molecular mechanisms involved in DYT- pathogenesis. gene encodes for protein PACT (Protein Activator of Protein Kinase R) individuals with mutations early-onset generalized dystonia. While precise linking neuronal etiology remain incompletely understood, research indicates such cause dysregulation signaling pathways cellular stress response as well production antiviral cytokines interferons (IFNs). focuses effect known functions PACT.

Language: Английский

Origin and Function of Anti-Interferon Type I Viral Proteins DOI Creative Commons
Marta Acchioni, Chiara Acchioni, John Hiscott

et al.

Virology, Journal Year: 2025, Volume and Issue: 605, P. 110456 - 110456

Published: Feb. 20, 2025

Language: Английский

Citations

0
Cell-type-specific requirement for TYK2 in murine immune cells under steady state and challenged conditions DOI Creative Commons

Anzhelika Karjalainen,

Agnieszka Witalisz‐Siepracka,

Michaela Prchal‐Murphy

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: March 2, 2025

Abstract Tyrosine kinase 2 (TYK2) deficiency and loss or inhibition of activity in men mice leads to similar immune compromised phenotypes, predominantly through impairment interferon (IFN) interleukin 12 family responses. Here we relate the transcriptome changes phenotypical observed TYK2-deficient ( Tyk2 −/− ) TYK2 kinase-inactive K923E naïve splenic cells upon ex vivo IFN treatment tumor transplant infiltration. The activities under homeostatic both challenged conditions are highly cell-type-specific with respect quantity quality transcriptionally dependent genes. major impact protein macrophages, NK CD8 + T tumor-derived cytolytic is on While reportedly partial IFN-I responses, identified IFN-I-repressed gene sets completely activity. Reported functions signaling crosstalk, metabolic cell differentiation maturation. None these phenotypes relates respective enriched types. Nonetheless, scaffolding capable change transcriptional at single levels chromatin accessibility promoter-distal regions cytokine most prominently cells. transcriptomic epigenetic effects shed new light biology this JAK member relevant for current future autoimmune inflammatory diseases inhibitors.

Language: Английский

Citations

0
Molecular mechanisms in DYT-PRKRA: pathways regulated by PKR activator protein PACT DOI Creative Commons

Tricia A. Simon,

Rekha C. Patel

Dystonia, Journal Year: 2025, Volume and Issue: 4

Published: March 13, 2025

Dystonia- PRKRA (DYT- ), 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 essential to characterize the underlying pathophysiology identify potential drug targets. This review summarizes recent studies that shed light on molecular mechanisms involved in DYT- pathogenesis. gene encodes for protein PACT (Protein Activator of Protein Kinase R) individuals with mutations early-onset generalized dystonia. While precise linking neuronal etiology remain incompletely understood, research indicates such cause dysregulation signaling pathways cellular stress response as well production antiviral cytokines interferons (IFNs). focuses effect known functions PACT.

Language: Английский

Citations

0