Proteostasis and Unfolded Protein Response Dynamics in Human Neuron and Mouse Glia Co-culture Reveal Cell-Specific Aging Responses.

ABSTRACT: Proteostasis, or protein homeostasis, is a tightly regulated network of cellular pathways essential for maintaining proper protein folding, trafficking, and degradation. Neurons are particularly vulnerable to proteostasis collapse due to their post-mitotic and long-lived nature and thus represent a unique cell type to understand the dynamics of proteostasis throughout development, maturation, and aging. Here, we utilized a dual-species co-culture model of human excitatory neurons and mouse glia to investigate cell type- specific, age-related changes in the proteostasis network using data-independent acquisition (DIA) LC-MS/MS proteomics. We quantified branch-specific unfolded protein response (UPR) activation by monitoring curated effector proteins downstream of the ATF6, IRE1/XBP1s, and P

SUBMITTER: Barny LA 

PROVIDER: S-EPMC12363859 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature