Figure 10. SRF connects neuronal activity–mediated gene transcription with autophagy in ALS MNs.

(A) In mSOD1 mice with SRF (black line), ALS-associated phenotypes such as body weight loss and impaired motor function appeared at around P90. This disease onset was shifted to approximately P50 in mSOD1 mice with SRF deletion (mSOD1/Srf KO; red line). At the disease endpoint, both cohorts were similar. (B) In mSOD1 mice, neuronal activity activates SRF-mediated gene transcription resulting in autophagic gene induction in MNs. This might facilitate removal of inclusions through autophagy and lysosomes, thereby improving neuronal survival. (C) In mSOD1/Srf-KO mice, loss of SRF limits the induction of an autophagy program by neuronal activity, thereby precipitating MN vulnerability. This contributes to impaired MN function and, subsequently, a premature disease onset.