A toxin known as β-N-methylamino-l-alanine (BMAA), which is found in blue-green algae, has been shown to cause proteins inside cells to clump together and cause cell death.
This finding suggests that BMAA may be a cause of neurodegenerative diseases like Alzheimer’s and MND and could lead to the development of new treatments.
What is BMAA?
BMAA is a non-protein amino acid. This means, that unlike the 20 amino acids that our bodies use to make proteins, it does not make a human protein.
BMAA is found in a type of bacteria called Cyanobacteria (more commonly known as blue-green algae), which are usually found in waterways as well as damp soil and on the roots of cycad plants.
Blue-green algae can occasionally cause algal blooms. This is when there is a rapid growth of organisms due to high levels of nutrients in the water. The resulting bloom can sometimes become so large that it can be toxic to wildlife.
What evidence suggests that BMAA may cause MND?
We know that MND is caused by a combination of subtle genetics, lifestyle and environmental factors. Although we know a number of genes that can cause MND, the evidence for lifestyle and environmental factors has been less convincing. To date few environmental factors have been identified that can cause proteins to clump inside cells and cause them to die.
BMAA was originally identified in Guam after the indigenous people (the Chamorros) were found to suffer from amyotrophic lateral sclerosis/parkinson’s dementia complex (ALS/PDC) at an increased rate compared to the general population (up to 100 times higher). When researchers investigated this previously they found that the Chamorros used seeds from cycad plants to make flour and regularly ate fruit bats. The fruit bats were found to also eat the seeds from the cycads and these were found to contain high levels of BMAA.
Last year there was an article published about the emerging science of BMAA, in which Dr Brian Dickie our Director of Research commented, “The recent finding that BMAA is mistaken for serine by tRNA synthetase during protein formation opens up a plethora of potential new studies in lab models of ALS, from yeast to mice, to see whether the formation of protein aggregates—the classic ‘hallmarks’ of motor neuron degeneration—can be replicated”. In essence, this is what this new research has now done.
If the article mentioned above is a bit daunting to digest, you can find a ‘potted’ version of the story in one of our blogs from the 2011 International Symposium on ALS/MND.
BMAA and its effect on cells
Research published today in the open access journal PLOS ONE further expands on the link between BMAA and MND.
The researchers found that when high concentrations of BMAA are present in neuron-like cells BMAA substituted itself with the amino acid L-serine during protein formation, creating a faulty protein within the cell. The faulty proteins were found to change shape so that they could no longer perform their role within the cell, causing them to clump together. The researchers also found that once BMAA was substituted into the protein this caused the cells to die.
This study further adds evidence to the role of BMAA and how it can cause proteins to clump together (which is a common hallmark in a number of neurodegenerative diseases). The researchers stated that:
‘Our finding that BMAA can be misincorporated(substituted) for serine in human proteins raises the possibility that such misincorporation results in neurodegenerative illness.’
What this means for the future
This research adds another piece to the BMAA puzzle and how it may cause neurodegenerative diseases like MND. The researchers have shown that BMAA can cause neuron-like cells to die but the next step would be for researchers to test this in motor neurones.
Dr Dickie also commented on this new research and what the next steps could be: “This research represents a key piece of evidence that takes the BMAA story forward, but it’s still not done and dusted. The next step is to see if they get the same results in human motor neurons in the lab, and not just ‘neuron-like’ cells. Many labs can create human motor neurons from iPSCs, so it would add weight to their theory if they can show that these motor neurons are vulnerable to BMAA – and indeed maybe those created from people with known genetic causes of MND are even more susceptible.”
If motor neurones are susceptible to BMAA this could then give rise to potential new treatments for MND that could block BMAA from substituting itself into human proteins.
Reference:
Dunlop RA, Cox PA, Banack SA, Rodgers KJ (2013) The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation. PLoS ONE 8(9): e75376. doi:10.1371/journal.pone.0075376
Twitter:
Lead author on the paper, Dr Rachael Dunlop, was kind enough to comment on the blog post via Twitter: “That blog is fantastic. Thanks for the clear concise explanation. Cheers. Brian Dickie’s comments are EXACTLY where we want to go next. If I can get a grant, then we will! #crossesfingers“
my dad died at the age of 79 with motor neurone.still cant get over it 3 years on.went into hospital for tests and died 5 weeks later after suspecting a stroke a year earlier.
Hi Ellen,
Our deepest condolences go out to you and your family, if you need to talk to anyone our MND Connect helpline on 08457 626 262 will be more than happy to speak to you. Alternatively if you want to talk about MND research please feel fee to contact us on 01604 611 880 or by emailing research@mndassociation.org.
Kindest regards,
Samantha
Research Development Team
MND Association, UK
My father, two of his brothers and his sister all died from MND. We need to find a cure for this terrible disease. Trinity College Dublin in Ireland are doing great work in the research arena. Please God we will have a breakthrough soon.
I would like to thank Samantha for an very accurate summary of our paper and Dr Dickie for his insightful comments. We are currently working with primary human motor neurons and will take these results forward to studies with cells from people with MND-related gene mutations. At this stage what might constitute a ‘susceptibility gene’ is really completely unknown.
Ken Rodgers
Is this part of the light at the end of the tunnel? It is a most welcome development and congratulations to all involved.
It is our job now to continue to both support those affected by the disease and to provide the Funds for research
My uncle, sister and brother all died from MND and my mother died from Frontal Lobar Dementia (caused by the same genetic anomaly that my other relatives had). We are hoping and praying that this breakthrough brings a treatment / prevention for MND. Should I and my family avoid suspected areas of blue-green algae or is it too soon to say.
Hi Stephen,
It’s too soon for us to say about whether people should avoid blue-green algae areas as this research has only shown that the toxin in blue-green algae causes ‘neuron-like cells’ to die. This research would need to be repeated in motor neurones to see if they exhibit signs of MND in order for us to know whether there is a definitive link.
It also sounds like a rare form of inherited MND may run in your family and the link with frontal lobar dementia has been shown with the gene C9orf72. We have some new information sheets on inherited MND, which you may find useful, and these can be found on our website: www.mndassociation.org/inheritedmnd. Alternatively I can post this information to you, please feel free to contact me via research@mndassociation.org or 01604 611 880.
Kindest regards,
Samantha
I have MND and believe I have had symptoms for approximately 2 years. I think I’m going quite well however I need the assistance of a walker to stand and my fine motor skills in my hands react badly to the cold weather.
No one in my family has had MND or any other associated condition.
I believe I have been exposed to blue algae and wondered whether there would be any advantage in taking serine to counteract the process?
Hi Michelle,
At present we still do not know the exact cause of MND as it is a complex disease. It is thought to be caused by a combination of lifestyle, environmental and subtle genetic factors and at present this research has only suggested that ‘neuron-like cells’ die when in the presence of a large amount of toxin produced by blue-green algae. This research would need to be repeated in motor neurones to see if they exhibit signs of MND in order for us to know whether there is a definitive link between blue-green algae and MND.
At present there has been no published research/ clinical trials that have shown a beneficial effect of taking serine in MND and because we still don’t know whether this toxin is linked to MND specifically there is no research to suggest that serine would counteract the process.
If you have any further questions please do not hesitate to contact me via research@mndassociation.org or 01604 611 880.
Kindest regards,
Samantha
Assume for a moment that the BMAA hypothesis is true. Is there any reason to believe that increasing dietary L-Serine would decrease incorporation of BMAA into motor neuron proteins? L-Serine is relatively safe and perhaps ALS patients should start taking it on an empirical basis.
Hi Robert,
As this work has only shown that BMAA can cause the proteins inside ‘neuron-like’ cells to clump together (a common hallmark of a number of neurodegenerative diseases) further work is needed to see if this occurs in motor neurones and specifically in MND models. If this is the case, researchers would then need to investigate if dietary L-Serine could be used. However, at present there is no evidence to suggest using this would be beneficial and further research is needed – but if people do want to try dietary L-Serine we recommend that they discuss this with their GP or neurologist as it may interfere with some medications.
Kind regards,
Samantha
The Research Team, MND Association, UK
email: research@mndassociation.org
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Fascinating. My sister has just recently been diagnosed with MND and I am trying to find out all about it. Don’t know of anyone else in my family who had MND but my father died from MS, which is also a neurological illness, when he was just 50 yrs old.He was a Bombadier Lance-Corporal in the Tank Regiment and developed MS after he had an accident and his tank hit a tree.I had polio, which is a virus, but has neurological effects. Would like to learn more.
Hi Elizabeth,
Thank you for your comment – if you’d like to learn more about MND visit www.mndassociation.org/research to find out about our current research and what we know about the disease. You can also subscribe to our research newsletter ‘what’s happening in MND research?’ if you wish to be kept up to date with the latest developments: www.mndassociation.org/whatshappeninginmndresearch.
Alternatively if you have any questions please do not hesitate to contact me on 01604 611 880 or research@mndassociation.org.
Best wishes,
Samantha Price, PhD
Research Information Co-ordinator
MND Association, UK
My father died of ALS after a 10 yr long battle. We have been friends of the Mass General Hospital Neuromuscular Lab director Dr. Robert H. Brown for years and have witnessed his dedication, perseverence in finding a cause and a cure and have also felt his love and compassion for my father during those terrible years.
If I had to look for a BMAA connection, I can tell you that my father was a horse race owner. I still remember many days during my childhood when I accompanied him to the track to whatch his horses train. The horse track combines humid soil, nitrogen from horse manure and sunshine, so it was probably a great place for blue green algae to form in the surface. As the horses train I assume this algae could have become volatile and breathable. The reason I suspect this as the cause for his disease is that his best friend, also a racehorse owner who was in the track with my father many times through the years also fell victim to ALS 3 years before my fathers onset.
I am curious as to wether horse jockeys have a higher incdence of ALS.
My heart goes to all those who suffer this terrible disease and their affected families. Its been 7 yrs since my father paseed away and I keep reading on ALS research waiting for the day I witness and end to this nightmare. It will be one of the happiest days in my life.
Dear Javier,
Thank you for your comment and your question about horse jockeys having a higher incidence of ALS. There is no research to suggest that horse jockeys have an increased risk of ALS and with regard to blue-green algae and BMAA, this has only been proven to be associated with ‘Parkinson’s Dementia complex – ALS’.
This research has shown that BMAA can cause cells to die, however, the next step would be to see if it causes motor neurones to exhibit signs of MND (to date this type of research has not been tested). Therefore at the moment this research indicates that BMAA may be a risk factor but more research is needed to confirm whether or not this is the case.
We are funding research that is trying to identify more of the causes of MND and from this we hope to understand more about the disease and how we can develop potential treatments.
If you have any questions please do not hesitate to contact me on research@mndassociation.org or 01604 611 880.
Kind regards,
Samantha Price, PhD
Research Information Co-ordinator
MND Association, UK
How or where do people get exposed to blue-green algae?
Hi Susan,
Blue-green algae often appear in stagnant lakes, which are located near fields where fertilisers are used. It is thought that people may get exposed to blue-green algae by living in close proximity to one of these ‘algae bloom’ lakes.
Kind regards,
Samantha
MND Association, UK
How is one to know whether algae is blue-green algar? I’ve a river near to my house that is covered in thick green algae. When I google blue-green algae it looks very similar. Would living near this be a risk factor or are the toxins only released through ingestion of contaminated water/plants/seafood/fish?
Hi Allie,
Strictly speaking blue-green algae is something called cyanobacteria, which is different to algae. But to explain the difference requires going into a lot of botany detail… I wouldn’t know how to tell the difference from sight alone.
Cyanobacteria tends to be the one responsible for large algal blooms, as mentioned in the above blog. However, even though this sort of algal bloom has been linked to a toxin called BMAA (thought to contribute to MND development) it is important to stress that not all algal blooms are toxic. The levels of BMAA in algal blooms can also vary considerably between sites and studies, with some cyanobacteria blue-green algal blooms having no BMAA detected.
Most of the research into BMAA and MND suggests that a way BMAA could enter the body is through someone’s diet. BMAA toxins can accumulate in the seeds of water plants, or in fish, or in the species higher up the food chain that eat these things. Direct contact with or ingestion of cyanobacteria algal-bloom water is being looked at as a risk factor too. Living in close proximity to algal blooms is not yet conclusively linked to increasing the risk of developing MND, as far as I am aware.
This is an ongoing area of research, which we continue to follow with interest. If you have any more questions on this please email research@mndassociation.org
Kind regards,
Sara Bolton
Research Development Team, MND Association UK