title: Gliotoxicity of the cyanotoxin, β-methyl-amino-L-alanine (BMAA).
abstract: The amino acid variant β-methyl-amino-L-alanine (BMAA) has long been associated with the increased incidence and progression of the amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC). Previous studies have indicated that BMAA damages neurons via excitotoxic mechanisms. We have challenged rat olfactory ensheathing cells (OECs) with exogenous BMAA and found it to be cytotoxic. BMAA also induces a significant increase in Ca2+ influx, enhanced production of reactive oxygen species (ROS), and disrupts mitochondrial activity in OECs. This is the first study investigating BMAA toxicity using pure glial cells. These findings align BMAA with the three proposed mechanisms of degeneration in ALS, those being non-cell autonomous death, excitotoxicity and mitochondrial dysfunction.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Chiu
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Gehringer
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Welch
authors.forename: Brett A
authors.initials: BA
authors.lastname: Neilan
mesh_terms: D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects*; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; D017382:Reactive Oxygen Species; C001824:beta-N-methylamino-L-alanine; D045022:Lactate Dehydrogenases; D002118:Calcium