Scientists and doctors know that the devastating disease spinal muscular atrophy (SMA) arises from a problem with both copies of the SMN1 gene, leading to a lack of the survival motor neuron (SMN) protein. But they don’t know why the lack of SMN protein causes spinal neurons to die, leading to muscle weakness in patients.
A new study implicates a key cellular mechanism as defective in SMA for the first time, providing a new lead for developing future interventions.
A study involving C. elegans worms (pictured) and human cells suggests that a deficiency of SMN protein leads to SMA by disrupting the important process of endocytosis.
Credit: Anne Hart/Brown University
The study also yielded a surprising twist: A mild version of the same defect may also confer resistance to infection in carriers of the disease for whom only one copy of the gene has lost function.
In the Proceedings of the National Academy of Sciences, corresponding author Anne Hart, professor of neuroscience at Brown University, and her team of researchers reported that that reduced levels of the SMN protein disrupt a cellular process called “endocytosis,” which all cells normally use to recycle and redistribute proteins and membranes. Endocytosis is especially important in nerve cells, called neurons, because they must also rapidly release neurotransmitters to communicate with each other and with muscles, across connections called synapses, Hart said.
“Without this specialised neurotransmitter rec