View source for Β-Methylamino-L-alanine

{{Redirect|BMAA}}
{{DISPLAYTITLE:β-Methylamino-<small>L</small>-alanine}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 437837247
| Name = β-Methylamino-{{small|L}}-alanine
| ImageFile = 3-Methylamino-L-alanine.svg
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageSize = 160
| ImageName = Stereo, skeletal formula of beta-methylamino-{{small|L}}-alanine (S)
| IUPACName = 3-(Methylamino)-{{small|L}}-alanine
| SystematicName = (2''S'')-2-Amino-3-(methylamino)propanoic acid<ref>{{cite web|title=alpha-amino-beta-methylaminopropionate - Compound Summary|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=105089|work=PubChem Compound|publisher=National Center for Biotechnology Information|access-date=25 April 2012|location=USA|date=19 August 2005|at=Identification}}</ref>
| OtherNames = 2-Amino-3-methylaminopropanoic acid
|Section1={{Chembox Identifiers
| CASNo = 15920-93-1
| CASNo_Ref = {{cascite|correct|??}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 108SA6URTV
| PubChem = 105089
| ChemSpiderID = 94816
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| KEGG = C08291
| KEGG_Ref = {{keggcite|changed|kegg}}
| MeSHName = alpha-amino-beta-methylaminopropionate
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 73169
| ChEMBL = 11488
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| SMILES = CNC[C@@H](C(=O)O)N
| StdInChI =1S/C4H10N2O2/c1-6-2-3(5)4(7)8/h3,6H,2,5H2,1H3,(H,7,8)/t3-/m0/s1
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = UJVHVMNGOZXSOZ-VKHMYHEASA-N
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
}}
|Section2={{Chembox Properties
| C=4 | H=10 | N=2 | O=2 
| LogP = −0.1
| pKa = 1.883
| pKb = 12.114
}}
|Section3={{Chembox Related
| OtherFunction_label = alkanoic acids
| OtherFunction = {{unbulleted list|[[Sarcosine]]|[[Dimethylglycine]]|[[Glycocyamine]]|[[Creatine]]|[[n-Methyl-D-aspartic acid|''N''-Methyl-{{sm|d}}-aspartic acid]]|[[Guanidinopropionic acid]]|[[Arginine]]}}
| OtherCompounds = [[Dimethylacetamide]]
}}
}}

'''β-Methylamino-{{small|L}}-alanine''', or '''BMAA''', is a [[non-proteinogenic amino acid]] produced by [[cyanobacteria]]. BMAA is a [[neurotoxin]]. Its potential role in various [[neurodegenerative disorder]]s is the subject of scientific research.

== Structure and properties ==
BMAA is a [[derivative (chemistry)|derivative]] of the amino acid [[alanine]] with a methylamino group on the [[side chain]]. This non-proteinogenic amino acid is classified as a [[Chemical polarity|polar]] base.

== Sources and detection ==
BMAA is produced by [[cyanobacteria]] in marine, freshwater, and terrestrial environments.<ref name=Cox>{{cite journal |vauthors=Cox PA, Banack SA, Murch SJ, Rasmussen U, Tien G, Bidigare RR, Metcalf JS, Morrison LF, Codd GA, Bergman B | year = 2005 | title = Diverse taxa of cyanobacteria produce b-N-methylamino-L-alanine, a neurotoxic amino acid | journal = PNAS | volume = 102 | issue = 14 | doi = 10.1073/pnas.0501526102 | pmid=15809446 | pmc=555964 | pages=5074–5078 | bibcode = 2005PNAS..102.5074C| doi-access = free }}</ref><ref name=Esterhuizen>{{cite journal |vauthors=Esterhuizen M, Downing TG | year = 2008 | title = β-N-methylamino-L-alanine (BMAA) in novel South African cyanobacterial isolates | journal = Ecotoxicology and Environmental Safety | volume = 71 | issue = 2 | doi = 10.1016/j.ecoenv.2008.04.010 | pmid = 18538391 | pages=309–313}}</ref> In cultured non-nitrogen-fixing cyanobacteria, BMAA production increases in a nitrogen-depleted medium.<ref name=Downing>{{cite journal |vauthors=Downing S, Banack SA, Metcalf JS, Cox PA, Downing TG | year = 2011 | title = Nitrogen starvation of cyanobacteria results in the production of β-N-methylamino-L-alanine 
| journal = Toxicon | volume = 58 | issue = 2 | pages = 187–194 | doi = 10.1016/j.toxicon.2011.05.017| pmid = 21704054 }}</ref> The biosynthetic pathway in cyanobacteria is unknown, but involvement of BMAA and its structural analog 2,4-diaminobutanoic acid (2,4-DAB) in environmental iron scavenging has been hypothesized.<ref>{{ cite journal |vauthors=Mantas MJ, Nunn PB, Codd GA, Barker D | year = 2022 | title = Genomic insights into the biosynthesis and physiology of the cyanobacterial neurotoxin 3-N-methyl-2,3-diaminopropanoic acid (BMAA) | journal = Phytochemistry | volume = 200 | page = 113198 | doi = 10.1016/j.phytochem.2022.113198 | pmid = 35447107 | bibcode = 2022PChem.200k3198M | s2cid = 248248698 | doi-access = free | hdl = 20.500.11820/31d20192-aa89-45b3-825f-165926f6f8c6 | hdl-access = free }}</ref><ref>{{ cite journal |vauthors=Mantas MJ, Nunn PB, Ke Z, Codd GA, Barker D | year = 2021 | title = Genomic insights into the biosynthesis and physiology of the cyanobacterial neurotoxin 2,4-diaminobutanoic acid (2,4-DAB) | journal = Phytochemistry | volume = 192 | page = 112953 | doi = 10.1016/j.phytochem.2021.112953 | pmid =  34598041 | bibcode = 2021PChem.192k2953M | s2cid = 238249735 | url = https://www.research.ed.ac.uk/en/publications/89c39093-6095-4158-b2b2-0eb895b79ee5 | hdl = 20.500.11820/89c39093-6095-4158-b2b2-0eb895b79ee5 | hdl-access = free }}</ref> BMAA has been found in aquatic organisms and in  plants with cyanobacterial [[Symbiosis|symbionts]] such as certain [[lichens]], the floating fern ''[[Azolla]]'', the leaf [[Petiole (botany)|petioles]] of the tropical flowering plant ''[[Gunnera]]'', [[cycad]]s as well as in animals that eat the fleshy covering of cycad seeds, including [[Pteropus|flying foxes]].<ref name=Vega>{{cite journal | author = Vega, A  |author2=Bell, A. | year = 1967 | title = a-amino-β-methylaminopropionic acid, a new amino acid from seeds of cycas circinalis | journal = Phytochemistry | volume = 6 |issue=5 | pages = 759–762 | doi=10.1016/s0031-9422(00)86018-5}}</ref><ref name=Banack>{{cite journal | author = Banack, SA |author2=Cox, PA | year = 2003 | title = Biomagnification of cycad neurotoxins in flying foxes: implications for ALS-PDC in Guam | journal = Neurology | volume = 61 | issue = 3 | pages = 387–9 | doi=10.1212/01.wnl.0000078320.18564.9f|pmid=12913204 |s2cid=38943437 }}</ref><ref name=Massaret>{{cite journal |vauthors=Masseret E, Banack S, Boumédiène F, Abadie E, Brient L, Pernet F, Juntas-Morales R, Pageot N, Metcalf J, Cox P, Camu W | year = 2013 | title = Dietary BMAA exposure in an amyotrophic lateral sclerosis cluster from Southern France
| journal = PLOS ONE | volume = 8 | issue = 12 | doi = 10.1371/journal.pone.0083406 | pmid = 24349504 | pmc = 3862759 | pages=e83406| bibcode = 2013PLoSO...883406M | doi-access = free }}</ref><ref name=Field>{{cite journal |vauthors=Field NC, Metcalf JS, Caller TA, Banack SA, Cox PA, Stommel EW | year = 2013 | title = Linking β-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD | journal = Toxicon | volume = 70 | pages = 179–183 | doi = 10.1016/j.toxicon.2013.04.010 | pmid = 23660330 }}</ref>

High concentrations (144 to 1836 ng/mg of flesh) of BMAA are present in shark fins.<ref>{{cite journal |author1=Kiyo Mondo |author2=Neil Hammerschlag |author3=Margaret Basile |author4=John Pablo |author5=Sandra A. Banack |author6=Deborah C. Mash | title = Cyanobacterial Neurotoxin β-N-Methylamino-L-alanine (BMAA) in Shark Fins | journal = Marine Drugs | date = 2012 | volume = 10 | issue = 2 | pages = 509–520| doi= 10.3390/md10020509|pmid=22412816 | pmc=3297012|doi-access=free }}</ref> Because BMAA is a neurotoxin, consumption of [[shark fin soup]] and cartilage pills therefore may pose a health risk.<ref name=ScienceDaily>{{cite web | url = https://www.sciencedaily.com/releases/2012/02/120223182516.htm | title = Neurotoxins in shark fins: A human health concern | date = February 23, 2012 | publisher = [[Science Daily]]}}</ref> The toxin can be detected via several laboratory methods, including [[liquid chromatography]], [[HPLC|high-performance liquid chromatography]], [[mass spectrometry]], [[Protein sequencing|amino acid analyzer]], [[capillary electrophoresis]], and [[NMR spectroscopy]].<ref name=Cohen>{{cite journal | author = Cohen, S.A. | year = 2012 | title = Analytical techniques for the detection of α-amino-β-methylaminopropionic acid | journal = Analyst | volume = 137 | issue = 9 | doi = 10.1039/c2an16250d | pmid = 22421821 | pages=1991–2005| bibcode = 2012Ana...137.1991C }}</ref>

== Neurotoxicity ==
BMAA can cross the [[blood–brain barrier]] in rats. It takes longer to get into the brain than into other organs, but once there, it is trapped in proteins, forming a reservoir for slow release over time.<ref>Mash D, et al. [http://www.abstracts2view.com/aan2008chicago/view.php?nu=AAN08L_P06.12  Neurotoxic non-protein amino acid BMAA in brain from patients dying with ALS and Alzheimer's disease]{{dead link|date=October 2016 |bot=InternetArchiveBot |fix-attempted=yes }} poster presented at: American Academy of Neurology Annual Meeting, Chicago, IL, 17 April 2008  ''Neurology'' 2008;70(suppl 1):A329.</ref><ref>Xie X, et al. [https://web.archive.org/web/20220331032759/http://www.mndassociation.org/research/for_researchers/international_symposium/22nd_international_symposium_on_alsmnd/abstract_book_2011.html Tracking brain uptake and protein incorporation of cyanobacterial toxin BMAA] abstract presented at: 22nd Annual Symposium on ALS/MND, Sydney, Australia, 1 December 2011.</ref>

=== Mechanisms ===
Although the mechanisms by which BMAA causes motor neuron dysfunction and death are not entirely understood, current research suggests that there are multiple mechanisms of action. Acutely, BMAA can act as an [[Excitotoxicity|excitotoxin]] on glutamate receptors, such as [[NMDA receptor|NMDA]], calcium-dependent [[AMPA receptor|AMPA]], and [[Kainate receptor|kainate]] receptors.<ref name=Weiss>{{cite journal |vauthors=Weiss JH, Koh J, Choi D | year = 1989 | title = Neurotoxicity of β -N-methylamino-L-alanine (BMAA) and β-N-oxalylamino-L-alanine (BOAA) on cultured cortical neurons | journal = Brain Research | volume = 497 | issue = 1 | doi = 10.1016/0006-8993(89)90970-0 | pmid = 2551452 | pages=64–71| s2cid = 140209787 }}</ref><ref name=Lobner>{{cite journal |vauthors=Lobner D, Piana PM, Salous AK, Peoples RW | year = 2007 | title = β-N-methylamino-L-alanine enhances neurotoxicity through multiple mechanisms | journal = Neurobiology of Disease | volume = 25 | issue = 2 | doi = 10.1016/j.nbd.2006.10.002 | pmid = 17098435 | pmc = 3959771 | pages=360–366}}</ref> The activation of the [[GRM5|metabotropic glutamate receptor 5]] is believed to induce oxidative stress in the neuron by depletion of [[glutathione]].<ref name=Rush>{{cite journal |vauthors=Rush T, Liu X, Lobner D | year = 2012 | title = Synergistic toxicity of the environmental neurotoxins methylmercury and β-N-methylamino-L-alanine | journal =    NeuroReport| volume = 23 | issue = 4 | doi = 10.1097/WNR.0b013e32834fe6d6 | pmid = 22314682 | pages=216–219| s2cid = 27441543 }}</ref>

BMAA can be misincorporated into nascent proteins in place of [[Serine|{{small|L}}-serine]], possibly causing protein misfolding and aggregation, both hallmarks of [[Neurofibrillary tangle|tangle diseases]], including [[Alzheimer's disease]], [[Parkinson's disease]], [[amyotrophic lateral sclerosis]] (ALS), [[progressive supranuclear palsy]] (PSP), and [[Lewy body disease]]. ''[[In vitro]]'' research has shown that protein association of BMAA may be inhibited in the presence of excess {{small|L}}-serine.<ref name=Dunlop>{{cite journal |vauthors=Dunlop RA, Cox PA, Banack SA, Rodgers JK | year = 2013 | title = The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation | journal = PLOS ONE | volume = 8 | issue = 9 | doi = 10.1371/journal.pone.0075376 | pmid=24086518 | pmc=3783393 | pages=e75376| bibcode = 2013PLoSO...875376D | doi-access = free }}</ref>

=== Effects ===
A study performed in 2015 with [[vervet monkey]]s (''Chlorocebus sabaeus'') in St. Kitts, which are homozygous for the [[Apolipoprotein|apoE4]] gene (a condition which in humans is a risk factor for Alzheimer's disease), found that vervets that were administered BMAA orally developed hallmark histopathology features of Alzheimer's disease, including [[amyloid beta]] plaques and [[neurofibrillary tangle]] accumulation. Vervets in the trial fed smaller doses of BMAA were found to have correlative decreases in these pathology features. Additionally, vervets that were co-administered BMAA with [[serine]] were found to have 70% less beta-amyloid plaques and neurofibrillary tangles than those administered BMAA alone, suggesting that serine may be protective against the neurotoxic effects of BMAA.

This experiment represents the first in-vivo model of Alzheimer's disease that features both beta-amyloid plaques and hyperphosphorylated tau protein. This study also demonstrates that BMAA, an environmental toxin, can trigger neurodegenerative disease as a result of a gene-environment interaction.<ref name="Cox and Davis">{{cite journal |vauthors=Cox PA, Davis DA, Mash DC, Metcalf JS, Banack SA | year = 2015 | title = Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain | journal = Proceedings of the Royal Society B | volume = 283 | issue = 1823 | doi = 10.1098/rspb.2015.2397 | pmid = 26791617 | pmc = 4795023 | page=20152397}}</ref>

Degenerative locomotor diseases have been described in animals grazing on [[cycad]] species, fueling interest in a possible link between the plant and the [[etiology]] of ALS/PDC. Subsequent laboratory investigations discovered the presence of BMAA. BMAA induced severe neurotoxicity in [[rhesus macaques]], including:<ref name=Spencer>{{cite book | last1=Spencer | first1=Peter S. | last2=Hugon | first2=J. | last3=Ludolph | first3=A. | last4=Nunn | first4=P. B. | last5=Ross | first5=S. M. | last6=Roy | first6=D. N. | last7=Schaumburg | first7=H. H.|editor-last1=Bock|editor-first1=Gregory|editor-last2=O'Connor|editor-first2=Maeve | title=Ciba Foundation Symposium 126 - Selective Neuronal Death| chapter=14: Discovery and Partial Characterization of Primate Motor-System Toxins | series=Novartis Foundation Symposia | publisher=Wiley Online Library | date=28 September 2007 | volume=126 | issn=1935-4657 | doi=10.1002/9780470513422.ch14| pmid = 3107939  | pages=221–238| isbn=978-0-470-51342-2 }}</ref>
*limb muscle [[atrophy]]
*nonreactive degeneration of [[anterior horn cells]]
*degeneration and partial loss of [[pyramidal neuron]]s of the [[motor cortex]]
*behavioral dysfunction
*[[Action potential|conduction]] deficits in the central motor pathway
*neuropathological changes of motor cortex [[Betz cell]]s

There are reports that low BMAA concentrations can selectively kill [[tissue culture|cultured]] motor neurons from mouse [[spinal cord]]s and produce [[reactive oxygen species]].<ref name=Lobner /><ref name=Rao>{{cite journal |vauthors=Rao SD, Banack SA, Cox PA, Weiss JH | year = 2006 | title = BMAA selectively injures motor neurons via AMPA/kainate receptor activations | journal = Experimental Neurology | volume = 201 | issue = 1 | doi = 10.1016/j.expneurol.2006.04.017 | pmid=16764863 | pages=244–52| s2cid = 24543858 }}</ref>

Scientists have also found that newborn rats treated with BMAA show a progressive neurodegeneration in the hippocampus, including intracellular fibrillar inclusions, and impaired learning and memory as adults.<ref name="KarlssonBerg2014">{{cite journal|last1=Karlsson|first1=Oskar|last2=Berg|first2=Anna-Lena|last3=Hanrieder|first3=Jörg|last4=Arnerup|first4=Gunnel|last5=Lindström|first5=Anna-Karin|last6=Brittebo|first6=Eva B.|title=Intracellular fibril formation, calcification, and enrichment of chaperones, cytoskeletal, and intermediate filament proteins in the adult hippocampus CA1 following neonatal exposure to the nonprotein amino acid BMAA|journal=Archives of Toxicology|volume=89|issue=3|year=2014|pages=423–436|issn=0340-5761|doi=10.1007/s00204-014-1262-2|pmid=24798087|pmc=4335130}}</ref><ref name="KarlssonRoman2009">{{cite journal|last1=Karlsson|first1=O.|last2=Roman|first2=E.|last3=Brittebo|first3=E. B.|title=Long-term Cognitive Impairments in Adult Rats Treated Neonatally with -N-Methylamino-L-Alanine|journal=Toxicological Sciences|volume=112|issue=1|year=2009|pages=185–195|issn=1096-6080|doi=10.1093/toxsci/kfp196|pmid=19692667|doi-access=free}}</ref><ref name=Karlsson3>Karlsson, O. (2011). Distribution and Long-term Effects of the Environmental Neurotoxin β-N-methylamino-L-alanine (BMAA): Brain changes and behavioral impairments following developmental exposure. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-140785</ref> BMAA has been reported to be excreted into rodent breast milk, and subsequently transferred to the suckling offspring, suggesting mothers' and cows' milk might be other possible exposure routes.<ref name="MantisAndersson2013">{{cite journal|last1=Andersson|first1=Marie|last2=Karlsson|first2=Oskar|last3=Bergström|first3=Ulrika|last4=Brittebo|first4=Eva B.|last5=Brandt|first5=Ingvar|title=Maternal Transfer of the Cyanobacterial Neurotoxin Î²-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring|journal=PLOS ONE|volume=8|issue=10|year=2013|pages=e78133|issn=1932-6203|doi=10.1371/journal.pone.0078133|pmid=24194910|pmc=3806833|doi-access=free}}</ref>

=== Human cases ===
{{missing information|section|dosage exposed to -- to help contextualize risk|date=September 2023}}
Chronic dietary exposure to BMAA is now considered to be a cause of the [[amyotrophic lateral sclerosis]]/[[parkinsonism]]–[[dementia]] complex (ALS/PDC) that had an extremely high rate of incidence among the [[Chamorros|Chamorro]] people of [[Guam]].<ref name=Cox2>{{cite journal |vauthors=Cox PA, Sacks OW | s2cid = 12044484 | year = 2002 | title = Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam | journal = Neurology | volume = 58 | pages = 956–9 | doi=10.1212/wnl.58.6.956 | pmid=11914415 | issue=6}}</ref>  The Chamorro call the condition [[Lytico-Bodig disease|''lytico-bodig'']].<ref name=Kurland /> In the 1950s, ALS/PDC prevalence ratios and death rates for Chamorro residents of Guam and [[Rota (island)|Rota]] were 50&ndash;100 times that of developed countries, including the United States.<ref name=Kurland>{{cite journal | author = Kurland, LK |author2=Mulder, DW | year = 1954 | title = Epidemiologic investigations of amyotrophic lateral sclerosis | journal = Neurology | volume = 4|issue=5 |doi=10.1212/wnl.4.5.355 |pmid=13185376 | pages=355–78|s2cid=44801930 }}</ref> No demonstrable [[heritable]] or [[virus|viral]] factors were found for the disease, and a subsequent decline of ALS/PDC after 1963 on Guam led to the search for responsible environmental agents.<ref name=Galasko>{{cite journal |vauthors=Galasko D, Salmon DP, Craig UK, Thal LJ, Schellenberg G, Wiederholt W | year = 2002 | title = Clinical features and changing patterns of neurodegenerative disorders on Guam, 1997-2000 | journal = Neurology | volume = 58 | issue = 1 | pages = 90–7 | doi=10.1212/wnl.58.1.90| pmid = 11781411 | s2cid = 24248686 }}</ref>  The use of flour made from cycad seed (''[[Cycas micronesica]]''<ref name=Hill>{{cite journal | author = Hill, K.D. | year = 1994 | title = The cycas rumphii complex (Cycadeceae) in New Guinea and the Western Pacific | journal = Australian Systematic Botany | volume = 7 | issue = 6 | pages = 543–567 | doi=10.1071/sb9940543}}</ref>) in traditional food items decreased as that plant became rarer and the Chamorro population became more Americanized following World War II.<ref name=Whiting>{{cite journal | author = Whiting, M.G. | year = 1963 | title = Toxicity of cycads | journal = Economic Botany | volume = 17 | issue = 4 | pages = 270–302 | doi=10.1007/bf02860136| s2cid = 31799259 }}</ref> Cycads harbor symbiotic [[cyanobacteria]] of the genus ''[[Nostoc]]'' in specialized roots which push up through the leaf litter into the light; these cyanobacteria produce BMAA.<ref>{{citation |author1=Rai, A.N. |author2=Soderback, E. |author3=Bergman, B. |year=2000 |title=Tansley Review No. 116 - Cyanobacterium-Plant Symbioses |journal=The New Phytologist |volume=147 |issue=3 |pages=449–481 |jstor=2588831 |doi=10.1046/j.1469-8137.2000.00720.x|pmid=33862930 |doi-access=free }}</ref>

In addition to eating traditional food items from cycad flour directly, BMAA may be ingested by humans through [[biomagnification]]. [[Flying fox]]es, a Chamorro [[delicacy]], forage on the [[sarcotesta|fleshy seed covering]] of cycad seeds and concentrate the toxin in their bodies. Twenty-four specimens of flying foxes from museum collections were tested for BMAA, which was found in large concentrations in the flying foxes from Guam.<ref name=Banack2>{{cite journal |vauthors=Banack SA, Murch SJ, Cox PA | year = 2006 | title = Neurotoxic flying foxes as dietary items for the Chamorro people, Mariana Islands | journal = Ethnopharmacology | volume = 106 | issue = 1 | pages = 97–104 | doi = 10.1016/j.jep.2005.12.032| pmid = 16457975 }}</ref> As of 2021 studies continued examining BMAA biomagnification in marine and estuarine systems and its possible impact on human health outside of Guam.<ref>{{cite journal | last1=Wang | first1=Chao | last2=Yan | first2=Chen | last3=Qiu | first3=Jiangbing | last4=Liu | first4=Chao | last5=Yan | first5=Yeju | last6=Ji | first6=Ying | last7=Wang | first7=Guixiang | last8=Chen | first8=Hongju | last9=Li | first9=Yang | last10=Li | first10=Aifeng | title=Food web biomagnification of the neurotoxin β-N-methylamino-L-alanine in a diatom-dominated marine ecosystem in China | journal=Journal of Hazardous Materials | volume=404 | year=2021 | issue=Pt B | issn=0304-3894 | doi=10.1016/j.jhazmat.2020.124217|doi-access=free | page=124217| pmid=33129020 }}</ref>

Studies on human brain tissue of ALS/PDC, ALS, [[Alzheimer's disease]], Parkinson's disease, [[Huntington's disease]], and neurological controls indicated that BMAA is present in non-genetic progressive neurodegenerative disease, but not in controls or genetic-based Huntington's disease.<ref name=Murch>{{cite journal |vauthors=Murch SJ, Cox PA, Banack SA | year = 2004 | title = A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam | journal = PNAS | volume = 101 | issue = 33 | pages = 12228–12231 | doi = 10.1073/pnas.0404926101| pmid = 15295100 | pmc = 514403 | bibcode = 2004PNAS..10112228M | doi-access = free }}</ref><ref name=Murchs>{{cite journal |vauthors=Murch SJ, Cox PA, Banack SA, Steele JC, Sacks OW | year = 2004 | title = Occurrence of b-methylamino-L-alanine (BMAA) in ALS/PDC patients from Guam | journal = Acta Neurologica Scandinavica | doi = 10.1111/j.1600-0404.2004.00320.x | pmid=15355492 | volume=110 | issue=4 | pages=267–9| s2cid = 32474959 | doi-access = free }}</ref><ref name=Pablo>{{cite journal |vauthors=Pablo J, Banack SA, Cox PA, Johnson TE, Papapetropoulos S, Bradley WG, Buck A, Mash DC | year = 2009 | title = Cyanobacterial neurotoxin BMAA in ALS and Alzheimer's disease | journal = Acta Neurologica Scandinavica | volume = 120 | issue = 4 | pages = 215–225 | doi = 10.1111/j.1600-0404.2008.01150.x| pmid = 19254284 | s2cid = 25385417 | doi-access = free }}</ref><ref name=Bradley>{{cite journal | author = Bradley, WG |author2=Mash, DC | year = 2009 | title = Beyond Guam: the cyanobacterial/BMAA hypothesis of the cause of ALS and other neurodegenerative diseases | journal =  Amyotrophic Lateral Sclerosis| volume = 10 | pages = 7–20 | doi = 10.3109/17482960903286009|pmid=19929726 |s2cid=41622254 }}</ref>

{{As of|2021}} research into the role of BMAA as an environmental factor in neurodegenerative disease continued.<ref name=Banack3>{{cite journal |vauthors=Banack SA, Caller TA, Stommel EW | year = 2010 | title = The cyanobacteria derived toxin beta-n-methylamino-L-alanine and Amyotrophic Lateral Sclerosis | journal = Toxins | volume = 2 | issue = 12 | pages = 2837–2850 | doi = 10.3390/toxins2122837| pmid = 22069578 | pmc = 3153186 | doi-access = free }}</ref><ref name=Holtcamp>{{cite journal | author = Holtcamp, W. | year = 2012 | title = The emerging science of BMAA: do cyanobacteria contribute to neurodegenerative disease? | journal = Environmental Health Perspectives | volume = 120 | issue = 3 | doi = 10.1289/ehp.120-a110 | pmid=22382274 | pmc=3295368 | pages=a110–a116}}</ref><ref>{{cite journal | last1=RA | first1=Dunlop | last2=SA | first2=Banack | last3=SL | first3=Bishop | last4=JS | first4=Metcalf | last5=SJ | first5=Murch | last6=DA | first6=Davis | last7=EW | first7=Stommel | last8=O | first8=Karlsson | last9=EB | first9=Brittebo | last10=AD | first10=Chatziefthimiou | last11=VX | first11=Tan | last12=GG | first12=Guillemin | last13=PA | first13=Cox | last14=DC | first14=Mash | last15=WG | first15=Bradley | title=Is Exposure to BMAA a Risk Factor for Neurodegenerative Diseases? A Response to a Critical Review of the BMAA Hypothesis | journal=Neurotoxicity Research | volume=39 | issue=1 | year=2021 | issn=1029-8428 | doi=10.1007/s12640-020-00302-0|doi-access=free | pages=81–106| pmid=33547590 | pmc=7904546 }}</ref>

== Clinical trials ==
Safe and effective ways of treating ALS patients with {{small|L}}-serine that has been found to protect non-human primates from BMAA-induced neurodegeneration, have been goals of clinical trials conducted by the Phoenix Neurological Associates and the Forbes/Norris ALS/MND clinic and sponsored by the Institute for Ethnomedicine.<ref name=Serine>[http://www.clinicaltrials.gov/ct2/show/NCT01835782?term=serine+als&rank=1 Determining the Safety of L-serine in ALS.]</ref><ref name=Zinc>[http://www.clinicaltrials.gov/ct2/show/NCT01259050?term=zinc+als&rank=1 Safety Study of High Doses of Zinc in ALS Patients] (completed).</ref>

== See also ==
* [[Oxalyldiaminopropionic acid]], a related toxin

== References ==
{{Reflist|2}}

{{Cyanotoxins}}
{{Neurotoxins}}

{{DEFAULTSORT:Methylamino-L-alanine, beta-}}
[[Category:2,3-Diaminopropionic acids]]
[[Category:Neurotoxins]]
[[Category:Cyanotoxins]]
[[Category:Toxic amino acids]]
[[Category:Secondary amino acids]]