Studying the Roles of Autophagy and TFEB in Krabbe Disease Pathogenesis
Krabbe disease (KD) is an inherited autosomal recessive lysosomal storage disorder (LSD ) that affects the central nervous system (CNS) and the peripheral nervous system (PNS). There is currently no cure for KD. The standard of care is hematopoietic stem cell transplant (HSCT), which delays disease onset. KD is caused by mutations in galactosylceramidase gene, that codes for the GALC enzyme. GALC is a lysosomal protein required for hydrolyzation of galactose ester bonds of galactosylceramide (GalCer), a major myelin component. Loss of GALC in defective myelin clearance, increased number of phagosomes and accumulation of galactosylsphingosine (psychosine) - a toxic metabolite of GalCer. My project aims to study the roles of autophagy and TFEB, master transcription factor of lysosome and autophagy components, in Krabbe disease pathology and pathogenesis.