Author ORCID Identifier
https://orcid.org/0009-0009-0553-6254
Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Biology
First Advisor
Jason Newton
Abstract
The correlation between incidences of neurodegenerative disease and exposure to the non-proteinogenic amino acid β-N-methylamino-L-alanine (BMAA), first observed in Guam in the 1950s, prompted an investigation of its neurotoxic effects. Further research linked BMAA exposure to neurodegenerative diseases characterized as amyotrophic lateral sclerosis- Parkinsonism-dementia complex (ALS/PDC); now mainly attributed to sporadic ALS (sALS). The mechanism of BMAA’s toxicity is not currently understood, with previous research focusing on its misincorporation during protein synthesis, this mechanism remains difficult to validate in vivo. Therefore, this thesis investigates an alternative mechanism in which BMAA disrupts de novo sphingolipid biosynthesis by substituting itself for L-serine and giving rise to atypical sphingolipid species. Using multiple model systems, this research shows that BMAA perturbs sphingolipid metabolism, induces developmental malformations, impairs locomotor behavior and growth, and contributes to central nervous system deficits at the motor axon level. This study further demonstrates that L-serine mitigates BMAA-associated developmental abnormalities and is neuroprotective of motor axon reduction in zebrafish embryos. In addition, LC-ESI-MS/MS analysis identifies novel sphingolipid species, 1-methylamino-dihydroceramides, consistent with the lipid incorporation mechanism of BMAA. Together, these findings support a mechanism of BMAA neurotoxicity mediated by incorporation in sphingolipid synthesis and provide evidence for L-serine as a protective modifier of these effects.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-8-2026
Included in
Cell Biology Commons, Developmental Biology Commons, Molecular and Cellular Neuroscience Commons