Figure 2.

Non-cell autonomous neurotoxicity in ALS. (a) Selective mutant SOD1 silencing demonstrated that mutant damage within motor neurons drives disease initiation^8,22,23, while mutant expression within neighboring microglia underlies rapid disease progression^7,8. The in vivo contributions of mutant SOD1 expression in astrocytes or Schwann cells are not yet established, while mutant expression in muscle does not contribute to disease⁵⁶. Consistent with non-cell autonomous mechanisms, selective mutant expression in either motor neurons^19,20 (b), astrocytes²⁹ (c) or microglia⁷ (d) alone are not sufficient to induce motor neuron degeneration.