What can a soybean worm teach us about neurodegenerative disease?

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis, though different conditions, are marked by the loss of neurons, with many researchers looking at the genetic cause of the unhealthy accumulation of toxic proteins to find ways to treat them. But, in a twist, agricultural scientists’ findings about a common soybean pest might offer fresh inspiration as a new model of regeneration.

A group of crop scientists at the University of Illinois at Urbana-Champaign studied soybean cyst nematode, or Heterodera glycines, an economically damaging pest of soybeans whose males happen to lose and then regain mobility as part of their natural life cycle. Using light and electron microscopy, the team examined the structural basis for that process in male H. glycines and published their findings in the journal PLOS Pathogens.

Following infection, both male and female soybean cyst nematodes experience muscle and neuron degeneration as they progress from a mobile juvenile stage to an immobile developmental stage. “During loss of mobility, the muscles shrink and separate away from the cuticle, or exoskeleton,” said Nathan Schroeder, Ph.D., an assistant professor in the Department of Crop Sciences at the University of Illinois and corresponding author of the study, in a statement.

The researchers examined the ventral nerve cord, whose motor neurons regulate the worm’s body wall muscles, and found a loss of neurons as it transitions to the immobile stage. In addition, they noticed a significant decrease of GABA, a neurotransmitter also critical for proper movement.

The magic happened in males at the adult stage, when they were able to move again and squirm through the soil in search of female mates. As the team discovered, H. glycines males underwent neuronal remodeling and saw their GABA levels increase as their muscle and associated neurons grew back.

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While the team acknowledged it may still be early to apply the findings to human neurodegenerative diseases, they appeared optimistic about worm's potential as a new model of regeneration.

“This is an animal that basically undergoes neurodegeneration, including nearly complete muscle atrophy, and then is able to reverse it in later development. From a human health perspective, I'm excited about the possibilities this could hold,” said Schroeder. “Let's not just think about the traditional model organism, the mouse, where you can simulate neurodegeneration in the lab. Instead, we can study what evolution has come up with in order to solve and reverse neurodegeneration.”

The regenerative medicine approach has been examined by scientists in diseases that compromise the central nervous system. Scientists at the University of Cambridge, for example, recently reprogrammed stem cells taken from skin to repair the protective myelin sheath around nerve cells. In mouse models of multiple sclerosis, the method successfully limited immune cells’ attack on the brain and spinal cord. Based on research from Case Western Reserve University, a startup called Convelo Therapeutics is developing drugs that help regenerate myelin.

Houston-based Celltex Therapeutics has partnered with Texas A&M Institute for Regenerative Medicine to use mesenchymal stem cell-derived exosome to reduce brain inflammation and repair neuronal damage related to Alzheimer’s disease.