Aptamers as Novel Inhibitors of the Neurotoxin Beta-methylamino-L-alanine (BMAA)

Exposure to specific environmental factors are believed to play a role in the development of many neural pathologies. Early studies linked chronic exposure to the Cyanobacteria biotoxin Beta methylamino-L-alanine (BMAA) ingestion of contaminated plant and animal tissue with the development of Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) within certain Indigenous populations of Guam and Japan. More recent studies in primate models and cell culture have further supported the association of BMAA with ALS/PDC. Taken together, the stage is set to explore in greater detail the relationship between BMAA and ALS/PDC at the cellular/molecular level. In this study, we propose to elucidate the mechanisms of BMAA- induced toxicity in cell culture through the use of cell functional assays, signaling pathway analysis, and global expression analysis in human cell lines. We further propose to develop and test the inhibitory potential of novel aptamers on BMAA’s activity in these cell lines. This study will provide mechanistic information regarding BMAA’s functions at the cellular level and provide data evaluating aptamers as a possible novel therapeutic for ALS/PDC. Future long-range experiments building on our generated data would investigate the mechanism and physiological effects of BMAA on specific identified signaling pathways and evaluate the use of aptamer- based therapeutics in animal models. Project Number: 1R15ES037888-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: Matthew Pawlus | Institution: BLACK HILLS STATE UNIVERSITY, SPEARFISH, SD | Award Amount: $484,122 | Activity Code: R15 | Study Section: Neurotoxicology and Alcohol Study Section[NAL] View on NIH RePORTER: https://reporter.nih.gov/project-details/11221509