NFE2L2 and amyotrophic lateral sclerosis: In conclusion, to confirm the role of ALDH1A2 in the mechanism of action of APG, our reversal experiments observed that knockdown of ALDH1A2 expression exacerbated OS, aldehyde accumulation and apoptosis in ALS mice or in vitro NSC34 cells, and inhibited the Nrf2/ARE signaling pathway (decreased expression of Nrf2, NQO1), while APG treatment not only attenuated OS and apoptosis in both in vivo and in vitro models of ALS, but also reduced the promotive effects of ALDH1A2 knockdown on ALS progression, further confirming that ALDH1A2 is positively regulated by APG to attenuate ALS progression.