蓝藻毒素L-BMAA的神经毒性有害结局路径研究进展OA

L-β-N-methylamino-L-alanine(L-BMAA)is a cyanobacterial toxin with neurotoxicity asso-ciated with the development of a range of neurodegenerative diseases,which has attracted increasing attention in recent years.Based on related studies from both domestic and international sources,this article reviews the sources,distribution,and neurotoxicity of the isomers of L-BMAA before investigating the mechanisms underlying L-BMAA-induced neurotoxicity based on the adverse outcome pathway(AOP)framework.Glutamate receptor overactivation,binding to neuromelanin,and misincorporation in-to proteins have been identified as molecular initiating events(MIEs)that can trigger key events(KEs)at the cellular level,including ion homeostasis imbalance,mitochondrial dysfunction,oxidative stress,protein misfolding and aggregation,inhibition of neuromelanin function,neuroinflammation,endoplas-mic reticulum stress,and neuronal apoptosis.All KEs ultimately lead to adverse outcomes(AOs),mani-fested as brain injury at the organ level,and motor dysfunction,memory deficits,and behavioral disor-ders at the individual level.Finally,this article summarizes the limitations to the current AOP framework and predicts priorities of research on the neurotoxicity of L-BMAA.