JAK1/2 inhibitor ruxolitinib reduces aggregates in cardiac proteinopathy

ABSTRACT: Misfolded proteins cause or contribute to a wide range of progressive diseases that are difficult to treat. Desmin-related (cardio-)myopathy (DRM), a well-studied proteinopathy, presents with progressive muscle weakness and shortened life span. Most DRM patients display intracellular accumulation of desmin and its chaperone αB-crystallin (CRYAB). Using an unbiased high-throughput screen, we found that Janus kinase 1 (JAK1) knockdown resulted in lower CRYABR120G aggregates in cardiomyocytes. Here, we tested whether the JAK1/2 inhibitor ruxolitinib ameliorates the disease phenotype in CRYABR120G DRM models. Ruxolitinib cleared pre-existing CRYABR120G aggregates in neonatal rat cardiomyocytes and human induced-pluripotent stem cell-derived cardiomyocytes, and enhanced ubiquitin-proteasome sys

SUBMITTER: Erda Alizoti 

PROVIDER: S-SCDT-10_1038-S44321-026-00411-X | biostudies-other |

REPOSITORIES: biostudies-other