Insights into L-BMAA-Induced Neuronal Injury :
Quest for Elucidating the role of GSK-3β in the Pathophysiology of ALS-PDC

Newsletter # 107



In vitro models


Over fifty years ago an epidemic of ALS was discovered on the Island of Guam where a disease complex of ALS (aka, Amyotrophic Lateral Sclerosis/Parkinson–Dementia Complex (ALS-PDC) was found to be one hundred times more prevalent than in the rest of the world. Several studies have pointed to the potential role of dietary exposure to the cyanobacteria-derived non-amino acid, β-Methylamino-L-alanine (L-BMAA) as a possible risk factor for ALS/PDC.
L-BMAA continues to hold significant interest as understanding its impact on neuronal health and its potential mechanisms of neurotoxicity could provide crucial insights into the common pathophysiology of these diseases.
The Neurofit investigations revealed that:
● L-BMAA induces injury in different neuronal populations, with spinal motor neurons showing a notably higher degree of damage when compared to neurons from other brain regions, including the cortex, mesencephalon, and hippocampus;
● the potential mechanisms underlying L-BMAA-mediated neuronal damage include the activation of a specific protein kinase, the Glycogen synthase kinase-3. Inhibition of this kinase effectively prevents L-BMAA-induced neuronal death.







It's noteworthy that GSK-3β activity serves as a converging point in the processes leading to the development of various neurofibrillary tangles and β-amyloid plaques associated with neurodegenerative diseases.
This pivotal insight underscores the potential of targeting GSK-3β as a therapeutic approach with broad implications for multiple neurodegenerative disorders 1.
1 https://doi.org/10.1016/j.bcp.2023.115923
  • Comparison of L-BMAA-induced cell injury in different types of neurons

    NEUROFIT website

    Left panel:
    Exposure of neurons with L-BMAA reduces in a dose-dependent manner the viability of different population types of neurons. The degree of susceptibility towards L-BMAA of the different types of neurons is in the following order: Spinal motor neurons, Cortical neurons, Hippocampal neurons, Mesencephalic neurons.

  • Involvement of GSK-3β pathway in the L-BMAA-induced neuronal injury

    NEUROFIT website

    Right panel:
    300 µM L-BMAA reduces by about 20% the viability of primary neurons in culture (white vs black column). GSK-3β inhibitors (A1070722 and TCS-2002) inhibit in a dose-dependent manner the neuronal injury induced by L-BMAA (black vs blue or green column).


NEUROFIT offers a range of validated in vitro and in vivo screening tests for psychiatry and neurology.

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