Sensory Neurons Have a Role to Play in ALS Research

Virginia Tech Carilion Research Institute scientists have shown that mutations in specific genes that destroy motor neurons and thereby cause the devastating effects of amyotrophic lateral sclerosis— also known as ALS or Lou Gehrig’s disease — also attack sensory neurons.

The discovery appearing in Scientific Reports indicates that studying sensory neurons could provide new mechanistic insights to prevent, slow, or even reverse ALS.

Virginia Tech Carilion Research Institute (VTCRI) scientists examined sensory neurons in cell cultures and in mice with ALS-causing mutant genes. They found that sensory neurons’ axons exhibit similar pathological changes found in motor neurons afflicted with ALS.

“Similar to motor neurons, ALS-inducing factors first affect the ending of sensory neuron axons, the site where they form synapses with other cells, and then the rest of the axon falls apart,” said Gregorio Valdez, an associate professor with the VTCRI and a faculty member in the Department of Biological Sciences in the College of Science at Virginia Tech. “Because sensory neurons are relatively easy to work with in a dish, in stark contrast to motor neurons, they are an attractive neuronal population for discovering and testing molecules to treat ALS.”

ALS has no cure, and most individuals with the disease die within three to five years from when symptoms first appear, according to the National Institute of Neurological Disorders and Stroke (NINDS).

“We’re closer to understanding where the problem starts within a given cell, and especially neurons, in ALS,” Valdez said. “However, we need to understand the reason such cells succumb to ALS-inducing factors. It is also important to develop and optimize assays to test molecules with the potential of preventing neurons from giving into ALS-inducing factors. Our findings show that sensory neurons could serve both purposes.”

In practice, motor neurons and sensory neurons work together. Sensory neurons constantly relay information, directly and indirectly, to motor neurons. This information could be about temperature, touch, and the contractile status of skeletal muscles. 

“In essence, we now have a high-content and high-throughput assay using sensory neurons in a dish to look for molecules that could prevent ALS-related pathology,” Valdez said.

This article has been republished from materials provided by Virginia Tech. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Vaughan, S. K., Sutherland, N. M., Zhang, S., Hatzipetros, T., Vieira, F., & Valdez, G. (2018). The ALS-inducing factors, TDP43A315T and SOD1G93A, directly affect and sensitize sensory neurons to stress. Scientific Reports, 8(1). doi:10.1038/s41598-018-34510-8