PUGNAc as a model for Sanfilippo Syndrome
Sciences and Mathematics, College of
Biology, Department of
BURS Faculty Advisor
Sanfilippo Syndrome is an autosomal recessive lysosomal storage disease (LSD) defined by a pathological accumulation of heparan sulfate. Sanfilippo Syndrome begins around 1 to 3 years of age with cognitive developmental delays, aggressive behavior, and speech impairments. Patients will regress to a vegetative state until death, usually 5 to 10 years after the onset of the disease. Sanfilippo Syndrome is caused by enzyme deficiencies in the degradation pathway of heparan sulfate resulting in the accumulation of heparan sulfate, which is thought to cause an inflammatory response leading to brain damage (O Fedele, 2015). Previous research in other lysosomal storage disorders demonstrates a loss of lysosomal tubulation in diseased cells. The lysosomal tubules are thought to help transport biomolecules from the lysosome. Lysosomal tubulation has yet to be observed in Sanfilippo Syndrome. It is hypothesized that cells of this disease will have decreased presence of lysosomal tubules. The decrease in tubules could result in the accumulation of heparan sulfate in the lysosome. It was observed that the lysosomal size was increased in the diseased state. A change in lysosome distribution was observed, with healthy cells having a more significant concentration near the nucleus and diseased cells having a more significant concentration in the cytoplasm. There also appears to be a decrease in tubulation in diseased cells.
Eisenga, Liz and Sterling, Felicity, "PUGNAc as a model for Sanfilippo Syndrome" (2023). Belmont University Research Symposium (BURS). 296.