Environmental Risks Associated with ß-N-methylamino-L-alanine (BMAA) and its Potential Causative Role in Amyotrophic Lateral Sclerosis (ALS)

Microbial toxins, specifically ß-N-methylamino-L-alanine (BMAA), are recognized as potential environmental causative agents of neurodegenerative diseases due to their ability to induce neurotoxicity. This multifaceted study elucidates the various neuropathological mechanisms triggered by BMAA and explores its broader implications in environmental health. By employing mass spectrometry-based proteomics (SWATH-MS) and Ingenuity Pathway Analysis (IPA), this research investigates the early effects of BMAA on Neuro2A cell lines. Despite showing no cytotoxic effects, BMAA significantly enhanced cell proliferation within a specific concentration range. Proteomic analysis revealed significant alterations in protein expression, particularly noting changes in neuronal development and mitochondrial function-related proteins. The study further investigates the potential for BMAA to cause DNA damage, focusing on telomere dysfunction and the subsequent activation of DNA damage response pathways. Additionally, the research incorporates a Design of Experiments (DoE) approach to assess the impact of various experimental conditions on DNA damage, demonstrating that treatment duration and cell culture conditions before BMAA exposure are critical factors influencing DNA damage. Immunocytochemistry studies complement these findings, highlighting the formation of ?H2AX foci in BMAA-exposed cells. This comprehensive analysis not only underscores the significant role of BMAA in environmental health but also provides insights into its complex biological interactions, thereby laying the groundwork for further investigations into its role in neurodegenerative pathologies.<p></p>