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Toxic load: blue-green algae’s role in motor neuron disease

Scientists have known for some time now that exposure to blue-green algae is linked to increased incidence of several neurodegenerative diseases. But the reason for the link has been a mystery until now…

Pretty but deadly: researchers now understand how blue-green algae is linked to neurodegenerative diseases. Mark Sadowski

Scientists have known for some time now that exposure to blue-green algae is linked to increased incidence of several neurodegenerative diseases. But the reason for the link has been a mystery until now. Research published in the journal PLOS ONE today may have the answer.

An algal toxin called BMAA has long been associated with the increased incidence of a motor neurone disease called amyotrophic lateral sclerosis (ALS). But for many years, the hypothesis suffered repeated blows as sceptics poked at the gaping hole in the theory – the lack of a plausible mechanism.

Now, a team of cell biologists and ethnobotanists, including myself, has revealed that BMAA mimics an amino acid that our bodies naturally use to make proteins called L-Serine. Mistaking the toxin for the amino acid, the body incorporates it into human proteins, rendering them harmful.

Because people can have low levels of exposure to BMAA over long periods, it can take between 10 and 15 years before ALS appears. But the time from diagnosis to death can be as short as 3 years.

How fruit bats in Guam provided clues

BMAA was first identified over 40 years ago, but was not linked to disease until ethnobotanist Paul Cox descended into the jungles of the Pacific island of Guam.

He was searching for the causes of a devastating neurological disease called amyotrophic lateral sclerosis/ Parkinson’s dementia like-complex (ALS/PDC), which had killed nearly half the adult indigenous population, the Chamorros.

BMAA was first identified in the jungles of Guam. NASA's Earth Observatory

Although about 20 genes have been linked to ALS, around 90% of cases are of unknown cause and there’s no cure. Predictably, a search for genetic causes on Guam quickly reached a dead end.

But the trip was not wasted. Cox noted that like Australian Aboriginals, the Chamorros relied heavily on the seeds of the cycad palm to make flour for tortillas and dumplings. Also like their Australian counterparts, they knew the unwashed flour contained a “poison” so they washed it thoroughly before use.

Cox and his colleague Sandra Banack found a neurotoxin in the flour, but it was in such low quantities that locals would need to consume over one tonne of it before they got sick.

Tasty but nasty treat

Also of interest to Cox and Banack was the Chamorros' voracious appetite for fruit bat coconut soup – a delicacy described by the locals as “like nothing you’ve ever tasted.”

The bats also ate the cycad seeds but curiously they had what appeared to be exorbitantly high levels of BMAA for what they consumed.

An analysis of their tissue found BMAA stuck to their proteins, enabling it to concentrate in their flesh; when the Chamorros ate the bats, they got a huge dose of BMAA.

Like Australian Aboriginals, the Chamorros used Cycad palm seeds to make flour. Pamla J. Eisenberg

This process, now termed “bioconcentration” has since been observed in shellfish, crustaceans and sharks. But how is it linked to neurodegeneration?

BMAA has been found in the brain tissue of ALS/PDC patients from Guam, as well as Alzheimer’s patients from North America. Other populations that also consume cycad flour – the Kii Peninsula of Japan and Western Papua New Guinea – have also experienced clusters of amyotrophic lateral sclerosis.

An elegant Google Maps analysis of New Hampshire in the United States tracked ALS patients to having lived by lakes or other bodies of water that were subject to frequent algal blooms.

Natural doesn’t mean safe

The idea that non-human amino acids can cause disease is not a new one; plants make thousands of mimics that have been linked to human and animal illnesses. Neurolathyrism, for example, is a permanent paralytic condition that predominantly occurs in famine-affected areas, and is caused by an unusual amino acid called ODAP.

In our lab, we’ve spent more than ten years looking at the drug used in Parkinson’s disease, called levodopa or L-DOPA, which is very similar to the human amino acid tyrosine.

Like BMAA, L-DOPA can also be “mis-incorporated” into our proteins, and also like BMAA, the resulting proteins do not fold correctly and build up as “junk” inside the cell over time. This “junk” eventually chokes the cell, sending it into programmed cell death or suicide.

An aerial photo of a blue green algae plume stretched across some 800km of the Murray River between Albury and west of Swan Hill, in north-west Victoria, April 2009. AAP

Cell suicide induced by misfolded proteins is now known to occur in a variety of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and importantly, ALS.

Blue-green algae and ALS

The size and frequency of algal blooms, which typically appear as a green carpet on lakes and rivers, is increasing with rising water temperatures and an excessive richness in nutrients in bodies of water, such as lakes (eutrophication).

Indeed, Australia is the proud owner of the largest fresh-water algal bloom, which occurred in the summer of 1991/1992 covering 1,200 kilometres of the Barwon-Murray basin. But if we’re all being exposed to BMAA, then why then do we all not have ALS?

With an incidence of about one in 100,000 ALS is relatively rare; exposure to BMAA alone does not appear to be sufficient to cause disease. Like many illnesses, it’s likely that ALS is a multifactorial condition requiring several factors to come together to trigger disease.

Research is beginning to point the finger at the role of poorly functioning recycling and refolding machinery in our cells. As these age, their function declines and likely contributes to neurodegenerative disorders.

BMAA might be just one factor in this devastating disease, but at least we now know how it might be causing toxicity. And because we have evidence for a role for BMAA replacing L-serine, these findings might go some way to developing a therapy. That is something for patients, many of whom have nothing.

Join the conversation

14 Comments sorted by

  1. Dave Hawkes

    Postdoctoral Researcher (Viral tools and Neuropeptides) at The Florey Institute of Neuroscience and Mental Health

    Fantastic study showing how collaborations between different fields of science result in ground breaking findings which will contribute to both our understanding of disease and hopefully provide information that leads to better/more effective treatment or prevention. Great work by Dr Rachie and her colleagues

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  2. John Holmes

    Agronomist - semi retired consultant

    I spent some time evaluating methods to kill native cycads in the Top End as cattle grazing on them were poisoned. Increasing the stocking rates using aerially seed legumes put more stock into the areas where the plants grew. Affected animals would show signs of failure of coordination of the hindquarter and made to run often would fall over. Not good for both the animal, nor the bystander watching on.

    There were also stories of some early settlers being poisoned when eating the cycads but…

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    1. Rachael Dunlop

      Post-doctoral fellow at University of Technology, Sydney

      In reply to John Holmes

      Hi John, yes, I have read about this, I have a review of toxic amino acids (also known as "non-protein amino acids" to indicate they're not preferentially used by humans) in the review process.

      The disease you refer to is known as "Zamia staggers" for the Zamia or burrawong palm (a type of cycad if my frazzled memory serves me correct).

      You've no doubt also heard of Birdsville Disease which is common in horses and manifests as them taking on a dejected appearance where they stand in the…

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    2. John Holmes

      Agronomist - semi retired consultant

      In reply to Rachael Dunlop

      Thanks.

      Have a look at books generally named "...Poisonous plants of...." to get a good overview of this issue. Tend not to see so many these days as once described, until some one sorts out the fine details of the toxicology, its been done, or we have cleared the areas where they were a problem. Also there are less people working in situations where time can be spent on such studies - got to have efficient focused research haven't we.

      I often pass over honey from Patterson's Curse or think twice about any consideration of using herbal preparations containing some common poisonous plants as the level of dosage is not able to be defined.

      If it is documented, the use of rumen contents from a goat in Hawaii to allow cattle to safely graze Leucaena is just one example of the complex interaction of grazing animals and toxins.

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    3. Sue Ieraci

      Public hospital clinician

      In reply to John Holmes

      Occasional cases of plant poisoning still turn up in EDs....oleander (cardiac glycosides), the occasional toddler who bites into the leaf of an arum family plant (calcium oxalate crystals).

      Teenagers concocting Angels Trumpet (atropine-like) seems to be less common - clearly there are more pleasant alternatives available.

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    4. Luke Weston

      Physicist / electronic engineer

      In reply to Ian Musgrave

      Whilst many microbial and animal toxins and venoms are complex proteins, many plant toxins are fascinating because many of the compounds evolution has produced in plants are remarkably diverse and potent drugs and toxins, and yet they are often surprisingly simple, very simple, molecules.

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  3. Sue Ieraci

    Public hospital clinician

    Yet another example of world-leading Australian science, even if it no longer rates a ministry...

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    1. Stewart D Simonson

      Chemical Engineer

      In reply to Laurie Thomas

      Based upon 2 years of Florida Wildlife Statistics, I am seeing a strong correlation (p-Value<0.01) for Null Hypothesis "No relationship between Doppler Pulsed Microwave Radar tower locations and locations of fish kills due to hypoxia, algae blooms and red tides. Guam has >30 megawatts of pulsed microwave radars. Chronic wasting in the US around White Sands Missile Range (>30 megawatts pulsed radars) and Indian River Lagoon in Florida around Cape Canaveral (>12 megawatts of pulsed microwave radars) lots of algae blooms, fish fying due to hypoxia, blue/brown algae and red tide. Research @ darkmattersalot

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