Self-destructing cells could hold key for brain health and food security

Brain cell and three-dimensional structure of SARM1 modelled with nicotinamide adenine dinucleotide. Credit: Hayden Burdett

Griffith University researchers have played a key role in investigating ‘cell suicide’ that could lead to treatments for neurodegenerative brain diseases and the development of disease-resistant plants.

Dr Thomas Ve, a lead researcher at Griffith University’s Institute for Glycomics and co-senior author on the new Science paper, used X-ray crystallography to determine the three-dimensional structure of the SARM1 protein, which is a central player in nerve fiber loss.

“Millions of people around the world are affected by neurodegenerative diseases like Parkinson’s, and the breakdown of brain cells is a common factor between them,” Dr Ve said.

“SARM1 is key to brain cell breakdown in various neurodegenerative diseases, so a greater understanding of this protein is an important step in the development of drugs that stop or limit this breakdown.”

Dr Ve worked closely with fellow Institute for Glycomics researcher and joint first author on the paper, Dr Yun Shi. The pair used NMR spectroscopy to explore functional features of the protein.

Dr Ve, also an Australian Research Council DECRA Fellow, said this new structural information about SARM1 had the potential to accelerate the development of drugs that target neurodegenerative diseases.

“We are very excited by these findings as they greatly advance our understanding of how SARM1 works at the molecular level,” Dr Ve said.

“It provides clues as to how one might target this protein using structure-guided approaches to block axon loss in neurodegenerative diseases.”

The SARM1 structure also revealed similarities to cell suicide triggering proteins in plants that provide resistance to many crop diseases, and the research team demonstrated that these proteins, like SARM1, can act as nucleotide-consuming enzymes.

A better understanding of cell death processes may also lead to the development of disease-resistant plants, helping boost yields, minimise waste and bolster food security.

Plant diseases account for more than 15 per cent of crops losses per year. Knowing how this process comes about in plants takes researchers a step closer to making effective synthetic resistance proteins that can be used to provide additional protection from crop diseases in Australia and the world.

The team used a combination of structural biology, biochemistry, neurobiology and plant science to analyse cells and proteins, laying the foundation for some potentially ground-breaking innovations.

Institute for Glycomics Director, Professor Mark von Itzstein AO, said this study provided exciting opportunities for the development of drugs to treat neurodegenerative disorders.

“There is an increasing urgency for such drugs given that the general global population is becoming older,” Prof von Itzstein said.

“The World Health Organization has predicted that neurodegenerative disorders, including those that affect motor function, will become the second-most prevalent cause of death in the next 20 years.”

It was led by researchers at Griffith University’s Institute for Glycomics, UQ, The Australian National University, and CSIRO, with a host of international collaborators in the US, UK and Australia.

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