Revealing How a Natural Compound May Affect Nerve Cell Protection in MS

25 July 2023

  • Azetidine-2-carboxylic acid (Aze), a plant-derived amino acid, can be mistakenly incorporated into proteins.
  • MS Australia-supported research shows that Aze-induced changes in protein structure may trigger the immune system to target and damage the protective myelin coating around nerve cells.
  • Scientists are exploring targeted interventions, such as using L-proline supplementation, to counteract the detrimental effects of Aze.

Investigating Plant Compound’s Potential Link to Nerve Cell Protection

In the world of nature’s chemistry, there are amino acids that go beyond the ones used for building proteins.

These special amino acids, known as non-protein amino acids (npAAs), are derived from plants and serve various protective functions, like defending against insects and competing plants.

One such npAA, azetidine-2-carboxylic acid (Aze), is found in beets and used for sugar production and livestock feed.

Recent research conducted by an interdisciplinary team at The University of Technology Sydney (UTS) suggests that Aze, due to its similarity to the amino acid proline, can be mistakenly incorporated into proteins during their formation.

This substitution could lead to changes in important proteins involved in creating myelin, the protective coating around nerve cells.

These altered proteins might trigger an immune response that mistakenly attacks and damages myelin, which is a key hallmark of MS.

What Did the Researchers Do?

MS Australia-funded researcher Associate Professor Alessandro Castorina and his team conducted experiments using specific microglial cells, which are immune cells in the brain associated with inflammation in MS.

They examined the effects of Aze on these cells by studying the levels of genes related to cellular stress and inflammation. The cells were treated with Aze alone or with a combination of Aze and L-proline, a natural amino acid similar to Aze.

What Did the Researchers Find?

The study revealed that Aze reduced cell viability and activated genes associated with cellular stress in microglial cells. Additionally, Aze altered the levels of specific markers related to an inflammatory state in these cells.

Moreover, the researchers discovered a significant increase in Aze-bound proteins after Aze treatment, confirming that Aze becomes a part of cellular structures.

However, when L-proline was given alongside Aze, it mitigated the negative effects. L-proline supplementation protected the cells from Aze-induced cell death, normalised levels of genes related to cellular stress, and reduced the amount of Aze incorporated into proteins.

What Does This Mean for People with MS?

These findings provide insights into a potential mechanism by which Aze, a non-protein amino acid found in certain plant-based foods, might contribute to the development or progression of MS.

When Aze is mistakenly incorporated into myelin proteins, it can lead to structural changes that trigger an immune response against the myelin coating.

Understanding how Aze affects myelin damage opens up possibilities for targeted treatments for MS.

The protective effects of L-proline supplementation suggest that it could be used as an intervention to counteract the harmful effects of Aze on microglial cells, potentially reducing the inflammatory response associated with MS.

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Revealing How a Natural Compound May Affect Nerve Cell Protection in MS