Examining The Effects of Dimethyl Fumarate on Relieving Oxidative Stress in Patient Cells with Neuronal Ceroid Lipofuscinosis (NCL)

Neuronal Ceroid Lipofuscinosis (NCL) is a group of severe neurological diseases, characterized as progressive encephalopathies that can be found in a subset of age groups: adult, juvenile and late infantile. This lysosomal storage disorder results from a deficiency in PPT1 enzyme - a lysosomal hydrolase which cleaves fatty acid chains, preventing proteins to be degraded, leading to the build up of protein within the cell. While the underlying molecular mechanism behind NCL remains poorly understood, the role of oxidative stress has been postulated as a downstream effect causing neurodegeneration. The efficacy of DMF as a possible pharmacological treatment to aid the downstream effects of oxidative stress caused by NCL mutation(s) was examined within this study. Cell cultures of a wild type, two different NCL2 and a NCL1 cell lines were maintained and treated with a vehicle control, 3uM of DMF or 30uM of DMF. Bradford assay and Western blot were conducted to quantify the protein concentration found within three NCL diseased cell lines as well as a wild type cell line. Immunofluorescent imaging was performed to quantify the number of vacuoles and lysosomes within the cell lines as well. Overall protein concentration decreased as a response to exposure to DMF. The number of vacuoles and lysosomes did not significantly change within diseased cell lines due to exposure to DMF. Collectively, these results suggest that DMF could play a role in relieving oxidative stress associated with NCL and support further investigation of the efficacy of this possible pharmacological treatment