New mechanism for protein misfolding may link to ALS

September 25, 2013, University of Technology, Sydney

Proteins play important roles in the human body, particularly neuroproteins that maintain proper brain function.

Brain diseases such as ALS, Alzheimer's, and Parkinson's are known as "tangle diseases" because they are characterized by misfolded and tangled proteins which accumulate in the brain.

A team of Australian and American scientists discovered that an unusual amino acid called BMAA can be inserted into neuroproteins, causing them to misfold and aggregate. BMAA is produced by cyanobacteria, that form scums or mats in or estuaries.

BMAA has been detected in the brain tissues of ALS patients.

In an article published in PLOS ONE scientists at the University of Technology Sydney and the Institute for Ethnomedicine in Jackson Hole, Wyoming, report that BMAA mimics a dietary aminoacid, L-Serine, and is mistakenly incorporated into neuroproteins, causing the proteins to misfold. The misfolded proteins build up in cells, eventually killing them.

"We found that BMAA inserts itself by seizing the transfer RNA for L-Serine. This, in essence, puts a kink in the protein causing it to misfold," says lead author Dr. Rachael Dunlop, a in Sydney working in the laboratory of Dr. Ken Rodgers.

"The cells then begin programmed cell death, called apoptosis. "Even more importantly, the scientists found that extra L-Serine added to the cell culture can prevent the insertion of BMAA into neuroproteins. The possibility that L-Serine could be used to prevent or slow ALS is now being studied."

Even though L-serine occurs in our diet, its safety and efficacy for ALS patients should be properly determined through FDA-approved clinical trials before anyone advocates its use," says American co-author Dr. Paul Cox.

In ALS, in the brain and spinal cord die, progressively paralyzing the body until even swallowing and breathing becomes impossible.

The disease is relatively rare but has affected a number of high-profile people including Professor Stephen Hawking and Yankee baseball player Lou Gehrig.

"For many years scientists have linked BMAA to an increased risk of motor neuron disease but the missing pieces of the puzzle relate to how this might occur. Finally, we have one of those pieces," said Dr Sandra Banack, a co-author on the paper.

Explore further: Neurotoxins in shark fins: A human health concern

More information: "The non-protein amino acid BMAA is misincorporated into human proteins in place of L-Serine causing protein misfolding and aggregation" dx.plos.org/10.1371/journal.pone.0075376

Related Stories

Neurotoxins in shark fins: A human health concern

February 23, 2012
Sharks are among the most threatened of marine species worldwide due to unsustainable overfishing. Sharks are primarily killed for their fins alone, to fuel the growing demand for shark fin soup, which is an Asia delicacy. ...

Staging system in ALS shows potential tracks of disease progression, study finds

June 19, 2013
The motor neuron disease Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, progresses in a stepwise, sequential pattern which can be classified into four distinct stages, report pathologists with the ...

Increased stability of a misfolded protein linked to age of onset of common form of motor neuron disease

April 22, 2013
Neurodegenerative diseases are characterized by the aggregation of misfolded proteins, which accumulate to form insoluble clumps within or around nerve cells. In the adult motor neuron disease amyotrophic lateral sclerosis ...

Receptor may aid spread of Alzheimer's and Parkinson's in brain

August 23, 2013
(Medical Xpress)—Scientists at Washington University School of Medicine in St. Louis have found a way that corrupted, disease-causing proteins spread in the brain, potentially contributing to Alzheimer's disease, Parkinson's ...

Neon exposes hidden ALS cells

April 30, 2013
A small group of elusive neurons in the brain's cortex play a big role in ALS (amyotrophic lateral sclerosis), a swift and fatal neurodegenerative disease that paralyzes its victims. But the neurons have always been difficult ...

How immune system, inflammation may play role in Lou Gehrig's disease

June 5, 2012
In an early study, UCLA researchers found that the immune cells of patients with amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, may play a role in damaging the neurons in the spinal cord. ALS is a disease of ...

Recommended for you

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

Male tobacco smokers have brain-wide reduction of CB1 receptors

August 15, 2018
Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor", when compared with non-smokers, reports a study in Biological Psychiatry.

Byproducts of 'junk DNA' implicated in cancer spread

August 14, 2018
The more scientists explore so-called "junk" DNA, the less the label seems to fit.

Doctors may be able to enlist a mysterious enzyme to stop internal bleeding

August 14, 2018
Blood platelets are like the sand bags of the body. Got a cut? Platelets pile in to clog the hole and stop the bleeding.

Artificial placenta created in the laboratory

August 14, 2018
In order to better understand important biological membranes, it is necessary to explore new methods. Researchers at Vienna University of Technology (Vienna) have succeeded in creating an artificial placental barrier on a ...

Using DeepMind's neural network learning system to diagnose eye diseases

August 14, 2018
Three institutions working together have applied DeepMind's neural network learning system to the task of discovering and diagnosing eye diseases. Moorfields Eye Hospital has been working with Google's DeepMind Health subsidiary ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.