Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Sep;8(9):3728-46.
doi: 10.3390/ijerph8093728. Epub 2011 Sep 16.

Does α-amino-β-methylaminopropionic acid (BMAA) play a role in neurodegeneration?

Affiliations
Review

Does α-amino-β-methylaminopropionic acid (BMAA) play a role in neurodegeneration?

Alexander S Chiu et al. Int J Environ Res Public Health. 2011 Sep.

Abstract

The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson's disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca(2+) influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential.

Keywords: ALS; Alzheimer’s; BMAA; PDC; Parkinson’s; cyanobacteria; cycad; excitotoxicity; glia; neural; neurodegeneration; neuron; toxicology.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The chemical structure of β-methylaminoalanine (BMAA).
Figure 2
Figure 2
Comparison of the structure of (A) β-carbamate (BMAA adduct) and (B) glutamtic acid (glutamate).
Figure 3
Figure 3
Illustrative summary of the modes of action of BMAA on neurons. In vivo, BMAA is present as a β-carbamate (represented by the blue dots), which binds to NMDA, AMPA and mGlu receptors (i). Activation of glutamate receptors results in an increase in the levels of Na+ and Ca2+ in the cell, accompanied by a reduction in K+ (ii). The cell becomes depolarised and the membrane becomes permeable, as illustrated by the dotted line, and combined with NMDA receptor activity, noradrenalin is released from the cell as a result (iii). The cysteine/glutamate antiporter system Xc is inhibited, as indicated by the red X (iv), leading to intracellular depletion of glutathione and an increase in ROS. This inhibition also causes an increase in the release of glutamate (v), which then binds to receptors to induce further excitotoxicity (vi). All these mechanisms combine to cause an increase in the generation of ROS (vii). The elevation of Ca2+ leads to overload of the mitochondria resulting in a massive release of cyt-c into the cytosol (viii).

Similar articles

Cited by

References

    1. Arnold A, Edgren DC, Palladino VS. Amyotrophic lateral sclerosis; fifty cases observed on Guam. J Nerv Ment Dis. 1953;117:135–139. - PubMed
    1. Kurland LT, Mulder DW. Epidemiologic investigations of amyotrophic lateral sclerosis. I. Preliminary report on geographic distribution and special reference to the Mariana Islands, including clinical and pathologic observations. Neurology. 1954;4:438–448. - PubMed
    1. Kurland LT, Mulder DW. Epidemiologic investigations of amyotrophic lateral sclerosis. I. Preliminary report on geographic distribution, with special reference to the Mariana Islands, including clinical and pathologic observations. Neurology. 1954;4:355–378. - PubMed
    1. Banack SA, Murch SJ, Cox PA. Neurotoxic flying foxes as dietary items for the Chamorro people, Marianas Islands. J Ethnopharmacol. 2006;106:97–104. - PubMed
    1. Whiting MG. Food Practices in Als Foci in Japan, the Marianas, and New Guinea. Fed Proc. 1964;23:1343–1345. - PubMed