Regarding ALS disease, the focus has traditionally been on motor neurons. However, recent research has revealed that abnormalities in interneurons are actually deeply involved in the onset and progression of ALS. Experimental evidence supporting this has increased and been published in numerous papers. Studies using animal models have shown that stress and dysfunction occur in the spinal cord interneurons at an earlier stage than when motor neurons begin to die.
Interneurons exist within the central nervous system, such as the brain and spinal cord. They connect sensory and motor neurons, or motor neurons to each other, playing an essential role in information processing, integration, inhibitory control, and reflex formation within neural circuits. In the motor cortex of the brain and the spinal cord, a decrease or dysfunction of inhibitory interneurons called GABAergic interneurons—which release GABA*1 and glycine*2—results in the loss of neural activity inhibition. This loss of inhibitory control causes excessive excitation of motor neurons (particularly pyramidal motor neurons). This leads to excessive calcium influx into the cells, damaging them and ultimately causing motor neuron death. This phenomenon is known as “glutamate toxicity,” also called excitotoxicity, and is considered to play a significant role in the pathogenesis of ALS.
*1 GABA stands for Gamma-Amino Butyric Acid. It is a type of neurotransmitter that calms the brain and spinal cord, inducing a relaxed state. It is produced within the brain and spinal cord from glutamate by the enzyme GAD.
*2 Glycine is a non-essential amino acid produced in the liver and kidneys. It is a major component of collagen and also an important component of blood. It is involved in the exchange of information within neural networks and plays a role in regulating bodily movements and sensations.
Animal studies indicate that enhancing the function of these inhibitory interneurons can delay ALS onset, reduce symptoms, and extend survival time, making them a promising new therapeutic approach. Furthermore, monitoring the health and condition of these interneurons is also being discussed as a potential biomarker for ALS disease. Some researchers mention in their papers that while ALS researchers have focused heavily on motor neurons for decades, “we have overlooked the very important interneurons right next to them, like the proverbial light under the lamp.” We sincerely hope this shift will lead to the discovery of new, more effective treatments more quickly than ever before.
https://pubmed.ncbi.nlm.nih.gov/39385724/
https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1434404/full
Reported by Nobuko Schlough @P-ALS in USA on Feb. 05, 2026
