Dear Colleagues,

The cyanobacterial metabolite β-N-methylamino-L-alanine (BMAA) has been proposed as a causative or contributory factor in the development of non-familial neurodegenerative diseases. The origin of this proposed link, commonly referred to as “The BMAA Hypothesis”, is the discovery of the amino acid BMAA as a component of the diet of the Chamorro people of Guam, who suffered from a very high incidence of Amyotrophic Lateral Sclerosis—Parkinsonism—Dementia Complex (ALS/PDC). Subsequent reports of BMAA in brain tissue of ALS/PDC and Alzheimer’s disease victims, appeared to support the hypothesis, and a relatively large body of in vitro and animal work, demonstrating acute neurotoxicity, was published, albeit at environmentally irrelevant exposure concentrations. Chronic animal exposure data are limited to a few reports, with at most a few months of exposure, and also at concentrations too high to represent environmental exposure. The absence of neuropathology or symptoms at environmentally relevant doses is one of the factors challenging the hypothesis. The environmental prevalence and potential human exposure risk also remain controversial topics, with widely disparate data in the literature both on the quantities of BMAA in the environment and the potential for exposure via inhalation and ingestion, and although an effort has been made to find spatial correlations between BMAA exposure and higher incidence of ALS, the low incidence of sporadic ALS makes finding adequate cases for such a study challenging. Research data on the potential link between cyanobacterial or BMAA exposure and either Alzheimer’s disease of Parkinson’s disease is absent in literature. The other vital component to support the BMAA hypothesis, is clarity on the mechanism of toxicity. Excitotoxicity and protein misincorporation have been suggested as mechanisms of toxicity, and although relatively weak excitotoxicity has been demonstrated for BMAA, misincorporation remains hypothetical. An understanding of how the exposure route or age, or exposure dose or dose regime, the systemic distribution and metabolic fate of BMAA, and the specific mechanism or mechanisms of toxicity, can result in the neuropathology and symptoms at the observed incidence of the relevant neurodegenerative diseases, is necessary to substantiate the link between BMAA and these diseases. The purpose of this Special Issue is therefore to highlight current research relevant to this link by focusing on environmental BMAA exposure route and exposure concentration, the geospatial link between exposure and disease, the systemic distribution and metabolic fate of ingested or inhaled BMAA, and the proposed mechanisms of BMAA neurotoxicity and associated pathologies in any model system. Manuscripts related to BMAA toxicology are therefore invited from all related fields and disciplines.

Prof. Dr. Tim Downing
Guest Editor

Note added by the Publisher: the Guest Editor was not involved in the editorial process for manuscripts on which they are authors. In this case, the editorial decisions were done by independent editorial board members.

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• BMAA
• β-N-methylamino-L-alanine
• exposure
• neurotoxicity
• neuropathology
• ALS
• ALS/PDC
• neurodegeneration