Figure 8.

Model for the non-cell-autonomous effect of mutant SOD1 on the activation of motoneuron selective death pathways. IFNγ produced by mutant astrocytes can selectively trigger death of some motoneurons through activation of the LIGHT-LT-βR pathway. IFNγ from circulating blood (serum) and the cerebrospinal fluid (CSF)⁴⁰ may also contribute to this neurodegenerative process. Motoneurons might represent an additional source of IFNγ that could participate to the inflammatory process. In grey, neurotoxic factors, including NO, or members of the TNF family, such as FasL, produced by mutant microglial cells and/or astrocytes, could also participate in the elimination of motoneurons in the disease.^{10, 14} Vulnerable motoneurons, having distinct intrinsic features, might be differentially susceptible to these non-cell-autonomous death triggers