ALS is a disease caused by motor neuron degeneration, however, it’s unclear what drives this neuronal degeneration. Recently, ALS researchers have begun to suspect that neurodegeneration in ALS occurs not only because of defects within motor neurons but also due to a convergence of defects in different non-neuronal and support cell types.
Thomas Jefferson University researchers from the Jefferson Weinberg ALS Center have been studying one of the brain’s “support cells” called astrocytes. In a recent study in the journal Glia, Piera Pasinelli, PhD, and colleagues found that astrocytes with a mutation in the gene FUS, known to be involved in ALS, can cause astrocytes to actively damage spinal cord neurons. It is the first demonstration that astrocytes gain toxic properties upon expression of this ALS mutation.
Astrocytes carrying the mutant form of the FUS protein increase the production of an inflammatory signal called tumor necrosis factor-alpha (TNFα). The increase in TNFα ultimately leads to damage and death of the motor neurons. When the inflammatory factor was blocked with antibodies in cellular models of ALS, the motor neuron viability was restored.
Future work will focus on gaining a deeper understanding of how this pathway is altered in ALS and how the communication between astrocytes and motor neurons can be targeted therapeutically.