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

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.

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