Neuropathological Mechanisms of β-N-Methylamino-L-Alanine (BMAA) with a Focus on Iron Overload and Ferroptosis.

Hamed Kazemi Shariat Panahi, Mona Dehhaghi, Benjamin Heng, Darius J R Lane, Ashley I Bush, Gilles J Guillemin, Vanessa X Tan

Journal: Neurotoxicity research 2022;40(2):614-635

PMID: 35023054

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Abstract

The incidence of neurodegenerative diseases and cyanobacterial blooms is concomitantly increasing worldwide. The cyanotoxin β-N-methylamino-L-alanine (BMAA) is produced by most of the Cyanobacteria spp. This cyanotoxin is described as a potential environmental etiology factor for some sporadic neurodegenerative diseases. Climate change and eutrophication significantly increase the frequency and intensity of cyanobacterial bloom in water bodies. This review evaluates different neuropathological mechanisms of BMAA at molecular and cellular levels and compares the related studies to provide some useful recommendations. Additionally, the structure and properties of BMAA as well as its microbial origin, especially by gut bacteria, are also briefly covered. Unlike previous reviews, we hypothesize the possible neurotoxic mechanism of BMAA through iron overload. We also discuss the involvement of BMAA in excitotoxicity, TAR DNA-binding protein 43 (TDP-43) translocation and accumulation, tauopathy, and other protein misincorporation and misfolding.

Address: Neuroinflammation Group, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.; Neuroinflammation Group, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.; PANDIS.Org, Bendigo, Australia.; Department of Microbial Biotechnology, School of Biology and Centre of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.; Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.; Neuroinflammation Group, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia. [email protected].; PANDIS.Org, Bendigo, Australia. [email protected].; Neuroinflammation Group, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.; PANDIS.Org, Bendigo, Australia.

DOI: 10.1007/s12640-021-00455-6

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https://dx.doi.org/10.1007/s12640-021-00455-6

MeSH Terms: Amino Acids, Diamino, Cyanobacteria, Cyanobacteria Toxins, Ferroptosis, Humans, Iron Overload, Neurodegenerative Diseases, Neurotoxins