Glucocerebrosidase mutations alter the endoplasmic reticulum and lysosomes in Lewy body disease.

ABSTRACT: Lewy body disease (LBD) development is enhanced by mutations in the GBA gene coding for glucocerebrosidase (GCase). The mechanism of this association is thought to involve an abnormal lysosomal system and we therefore sought to evaluate if lysosomal changes contribute to the pathogenesis of idiopathic LBD. Analysis of post-mortem frontal cortex tissue from 7 GBA mutation carriers with LBD, 5 GBA mutation carriers with no signs of neurological disease and human neural stem cells exposed to a GCase inhibitor was used to determine how GBA mutation contributes to LBD. GBA mutation carriers demonstrated a significantly reduced level of GCase protein and enzyme activity and retention of glucocerebrosidase isoforms within the endoplasmic reticulum (ER). This was associated with enhanced expressio

SUBMITTER: Kurzawa-Akanbi M 

PROVIDER: S-EPMC3494984 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature