There is increasing evidence for a role of the neighboring non-neuronal cells in ALS. Under normal conditions, glial cells provide nutritional and trophic support to MNs, but in ALS, they appear to exacerbate neurodegeneration in a non-cell autonomous fashion. These cells include microglia, astrocytes, oligodendrocytes and Schwann cells. Limiting the expression of mutant SOD1 to MNs only does not lead to neurodegeneration in mice (Pramatarova et al., 2001; Lino et al., 2002), and chimeric mouse studies have established that the presence of mutant SOD1G93A in glial cells induces neurodegeneration and MN loss (Papadeas et al., 2011). Both microglia and astrocytes appear to enhance disease progression by inducing neuroinflammation, whereas oligodendrocytes drive disease initiation. Non-neuronal cells may also be involved in the spread of pathological proteins in ALS (Thomas et al., 2017; Porta et al., 2018). However, whilst misfolded proteins released by MNs can be taken up by glial cells, they may be less toxic to these cells than to MNs (Benkler et al., 2018).