Integrated Stress Response Signatures Drive Monocyte Dysfunction in <i>GBA1</i>- and <i>LRRK2</i>-Linked Parkinson's Disease.

ABSTRACT: Monocytes are increasingly implicated in Parkinson's disease (PD) pathogenesis, with idiopathic cases showing mitochondrial and lysosomal dysfunction. However, the impact of PD-associated mutations on monocytes remains unclear. To address this, we investigated transcriptomic and functional disturbances in peripheral monocytes from patients with GBA1- and LRRK2-associated PD and idiopathic PD. Transcriptomic data revealed shared and mutation-specific signatures, including those related to immune dysregulation, and consistent defects in lysosomal and mitochondrial pathways. Network and pathway analyses further uncovered downregulation in protein translation and enrichment of integrated stress response (ISR) signatures, alongside aberrant expression of genes linked to ER stress,

SUBMITTER: Mattei D 

PROVIDER: S-EPMC12633084 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature