In the quest to understand the driving forces behind neurodegenerative diseases, researchers in recent years have zeroed in on clumps of malfunctioning proteins thought to kill neurons in the brain and spinal cord by jamming their cellular machinery. In a new study published in the journal Structure, researchers announced the first evidence that stabilizing a protein called SOD1 can help reverse this process in the types of neurons affected by the fatal neurodegenerative condition Amyotrophic Lateral Sclerosis (ALS). Also known as Lou Gehrig’s disease, ALS has no cure and its causes remain largely mysterious.

In addition to showing that stabilizing SOD1 is protective for motor neuron-like cells, the new study is also the first to demonstrate a way to mutate disease-associated SOD1 in order to stabilize it, offering exciting new leads for finding drugs that could potentially prevent the disease or slow its progression.

The findings could be particularly relevant to a subset of ALS cases – an estimated 1 to 2 percent – that are associated with variations in the SOD1 protein. However, SOD1 has been implicated in toxic clump formation even in patients without mutations in their SOD1 genes, suggesting that stabilizing the protein could benefit many other patients as well.

Paper: “A Phosphomimetic Mutation Stabilizes SOD1 and Rescues Cell Viability in the Context of an ALS-Associated Mutation”

Reprinted from materials provided by UNC Health Care.


October 13, 2016