New research provides clues about the biological features of cells in the spinal cord vulnerable to ALS

February 11, 2023 | Biology

The pathology of amyotrophic lateral sclerosis (ALS) involves selective degeneration of motor neurons in specific areas of the spine, brainstem, and cortices. The underlying mechanism of the degeneration is still unclear, but existing evidence suggests many factors including oxidative damage, excitotoxicity, apoptosis, and abnormal neurofilament function, among others.

Published in Neuron, a group of experts funded by the National Institutes of Health (NIH) discovered a link between a motor neuron’s large cell size and the supporting structure with the genes that underlie their susceptibility to degeneration in ALS.

The study yields a catalog or an ‘atlas’ that specifies the various communities of cell types within the human spinal cord. The researchers determined dozens of cell types and examined their molecular profiles by analyzing their gene expression at the single-cell level. They exhibited the functionality of the atlas by studying closely motor neurons, which provide voluntary movement and motor control.

A set of genes that determines the size of the motor neuron cell body and its extended axon also happens to underlie their susceptibility to degeneration. The motor neuron’s molecular profile was defined by the genes involved in its cytoskeleton structure, neurofilament, and the genes linked to the onset of ALS.

Further experiments exhibited how ALS-related genes are also in motor neurons of mice. This research gives insight into ALS and demonstrated the utility of the spinal cord cell atlas in studying pathology and disease and the development of possible interventions.