Galc-KO Mouse

GALC, encoding galactosylceramidase, is a gene of great significance. Galactosylceramidase is a lysosomal enzyme pivotal in the glycosphingolipid metabolism pathway [1,3]. Mutations in GALC can lead to Krabbe disease, also known as globoid cell leukodystrophy, a lysosomal storage disease [2,3,4,5,6,7,8].

In research, GALC knockout using CRISPR-Cas9 in neuronal cell models did not lead to alpha-synuclein accumulation, suggesting that increased rather than reduced galactosylceramidase levels may be associated with Parkinson's disease. The common variant p.I562T may affect the maturation and activity of galactosylceramidase [1]. In a mouse model of Krabbe disease, brain-targeted AAV1-GALC gene therapy reduced psychosine levels and extended lifespan [6]. Also, rAAV2-GALC rescued GALC enzymatic activity in neural stem cells derived from Krabbe patient-induced pluripotent stem cells [7].

In conclusion, GALC is crucial for normal glycosphingolipid metabolism. Its deficiency is linked to Krabbe disease. Studies using gene-modified models, like knockout in neuronal cells and gene-therapy-based approaches in mouse models, have provided insights into GALC's role in Parkinson's disease and Krabbe disease, enhancing our understanding of related disease mechanisms and potential treatment strategies.