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Unexpected consequences of combined glucocerebrosidase and acid sphingomyelinase deficiency in a model of Parkinson’s disease

ABSTRACT: Heterozygous variants in GBA1, encoding glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson’s disease (PD). Moreover, sporadic PD patients also have a substantial reduction of GCase activity. Genetic variants of SMPD1 are also overrepresented in PD cohorts, whereas a reduction of its encoded enzyme (acid sphingomyelinase or ASM) activity is linked to an earlier age of PD onset. Despite both converging on the ceramide pathway, how the combined deficiencies of both enzymes might interact to modulate PD has yet to be explored. Therefore, we created a double-knockout (DKO) AQ4 zebrafish line for both gba1 (or gba) ¶ and smpd1 to test for an interaction in vivo, hypothesising an exacerbation of phenotypes in the DKO line compared to those for single mutants

ORGANISM(S): Danio rerio

PROVIDER: GSE229995 | GEO | 2023/04/24

REPOSITORIES: GEO

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