Approximately 5,000 people in the U.S. develop amyotrophic lateral sclerosis (ALS) each year.
On average, they survive for only two to five years after being diagnosed, according to the Centers for Disease Control and Prevention. The rapidly progressing neurodegenerative disease causes the death of neurons in the brain and spinal cord, resulting in muscle weakness, respiratory failure and dementia. Despite the devastating nature of the disease, little is known about what first triggers the deterioration of motor neurons at the onset of ALS.
Now, researchers from University of California San Diego and their colleagues report that they have identified a key pathway that sets off neurodegeneration in the early stages of the disease. The findings could lead to development of therapies to prevent or slow the progression of ALS early on, before major damage has been done. The study was published on October 31, 2024 in Neuron .
A protein called TDP-43 is usually located in the nucleus of motor neurons, where it regulates gene expression required for the cells to function. Studies have shown that when TDP-43 instead accumulates in the cytoplasm, outside of the nucleus, it is a telltale sign of ALS. How the protein ends up in the wrong place, leading to neuronal degeneration, has stumped researchers until now.
By the time you see a patient with ALS and you see the TDP-43 protein aggregated in the cytoplasm, it's like the accident site with all the cars crashed already, but that's not .