Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of upper motor neurons in the brain and lower motor neurons extending from the spinal cord to muscles. A recent study revealed that immune cells are activated by neuronal changes in individuals with ALS (Figure 1). By using a genetically modified mouse model, researchers observed that structural alterations in upper neurons precede the onset of ALS symptoms.
The study suggests that these morphological changes signal microglia and astrocytes, the immune cells of the central nervous system. While their initial arrival is protective, prolonged presence becomes toxic to neurons, reducing synaptic connections between motor neurons in the brain and spinal cord, ultimately leading to muscle atrophy and loss of motor function.
In experiments, a semi-synthetic drug derived from Withaferin A, an extract of the Ashwagandha plant, was tested. This drug effectively inhibits inflammation, allowing motor neurons to revert to a more normal state. The researchers observed neuronal regeneration in the absence of activated immune cells. This finding suggests a potential therapeutic approach for ALS by targeting inflammation to alleviate symptoms and promote neuron recovery.
Journal article: Mari Carmen Pelaez, M.C., et al., 2023. Neuronal dysfunction caused by FUSR521G promotes ALS-associated phenotypes that are attenuated by NF-κB inhibition. Acta Neuropathologica Communications.
Summary by Stefan Botha