Lipid Storage Disorders: The Case Of Gaucher's Disease
Sciences and Mathematics, College of
Biology, Department of
BURS Faculty Advisor
Gaucher's Disease is an autosomal recessive disease that impacts the lysosomal gene GBA, which encodes for glucocerebrosidase. As a result, the lysosomes cannot break down glycolipids; thus, lysosomal glycolipid accumulation occurs. This lysosomal storage disease (LSD) generally has symptoms of spleen, liver, and bone marrow enlargement and dysfunction; fatty materials can also build up in the brain, lungs, and other organs. Depending on which of the three types of Gaucher's Disease, the onset ranges between early infancy, childhood, adolescence, and adulthood. In Type 2, Gaucher's can induce neurodegeneration which can be fatal. ¹
Current studies suggest that the degradation of glycolipids is mediated by internalization by endocytosis. The glycolipid transfer protein (GLTP) transports glycolipids to the lysosomes, where they are degraded. ² Niemann Pick Type C1 Disease (NPC) is another disorder that impacts glycolipid transport. Previous work on NPC disease demonstrates that tubulation is presumed to play a role in transporting cholesterol. Furthermore, researchers discovered that cells that lacked lysosomal tubules also exhibited an accumulation of cholesterol in lysosomes. ³
In this study, we induced Gaucher's Disease with a known GBA antagonist, Conduritol B Epoxide (CBE), and investigated lysosomal activity via Immunofluorescence Microscopy and Live Cell Imaging. We hypothesized that lysosomal tubulation is also inhibited in Gaucher's Disease. This insight may help illustrate all factors or consequences regarding a mutated GBA gene. The results exhibited increased lysosome size and lack of tubulation in the drugged cell line.
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Alammuri, Osayd, "Lipid Storage Disorders: The Case Of Gaucher's Disease" (2023). Belmont University Research Symposium (BURS). 330.