Characterization of Neutral Sphingomyelinase in Plasma and PBMCs and the Role of Sphingolipid Enzymes in Pathology.

Open Access
Author:
Dobson, Jennifer Lauren
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Stephen Wade Schaeffer, Thesis Supervisor
  • Richard Cyr, Honors Advisor
Keywords:
  • Sphingolipid enzymes
  • sphingolipid pathway
  • neutral sphingomyelinase
  • Neurodegenerative diseases
  • psychiatric disorders
Abstract:
The balance of sphingolipid enzymes is critical for normal physiological mechanisms. Specifically acid and neutral sphingomyelinase play important roles in maintaining the balance for cell proliferation and apoptosis. Acid sphingomyelinase and Neutral sphingomyelinase hydrolyze sphingomyelin to ceramide and play key roles in regulating sphingolipid metabolism and determining cell fate. A number of research studies show their role in neuropathology. Specifically increased levels of ASM are serum were recorded in dementia, Alzheimer’s disease, major depressive disorder, and multiple sclerosis. Since then, it has been of further interest to determine the activity of other sphingolipid enzymes in neuropathology and also measure acid sphingomyelinase in cerebrospinal because of its close proximity to brain regions. ASM was characterized in cerebrospinal fluid in 2013 but clinical samples have not yet been tested. In this research, an analysis of ASM activity in cerebrospinal fluid was conducted in a clinical study comparing patients with multiple sclerosis to healthy controls. Additionally before this research, the sphingolipid enzymes, neutral sphingomyelinase had not been characterized in human blood samples. An enzyme assay was developed and optimized to measure neutral sphingomyelinase activity in PBMCs and serum and was then tested in patients with alcohol dependency. The results of these studies provide insights into the roles of sphingolipid enzymes in pathology.