Cathepsin B deficiency disrupts cortical development via PEG3, leading to depression-like behavior.

ABSTRACT: Cathepsin B (CatB), a protease in endosomal and lysosomal compartments, plays a key role in neuronal protein processing and degradation, but its function in brain development remains unclear. In this study, we found that CatB is highly expressed in the cortex of E12.5-E16.5 mice. Morphological analysis revealed significant defects in cortical development in CatB knockout (KO) mice, particularly in layer 6. In vitro experiments showed that CatB deficiency notably impaired neuronal migration and development. Behaviorally, CatB KO mice displayed prominent depressive-like behaviors, and electrophysiological recordings demonstrated significantly reduced neuronal activity in layer 6 of the medial prefrontal cortex. Mechanistically, proteomics analysis revealed that CatB KO affected neuronal migr

SUBMITTER: Xie Z 

PROVIDER: S-EPMC12287434 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature