Fig. 4: Mitophagy stimulation restores memory deficit and abrogates pathologies in AD-like Aβ worms, and regulates cellular Aβ production in mouse neuroblastoma cells.
a, Effects of Kaem and Rhap on associative memory in adult day 1 WT and hAβ1–42 (CL2355) worms. Data were pooled from at least 4 biological replicates. b, Effects of Kaem and Rhap on designated gene expression in day 1 adult worms. Data are from 1 representative biological repeat (3 technical repeats) from a total of 3 biological replicates. c, Left: effects of pink-1, pdr-1, dct-1, sqst-1 and bec-1 on Kaem- and Rhap-dependent memory improvement in the hAβ1–42 (CL2355) worms. Right: effects of Kaem and Rhap on associative memory in adult day 1 hAβ1–42Glu;hApoE3Glu (UA353) and hAβ1–42Glu;hApoE4Glu (UA355) worms. ‘Glu’ denotes that either hAβ1–42 or hApoEs were expressed only in the glutamatergic neurons. Data were pooled from at least 4 biological replicates. d, Effect of Kaem or Rhap on glutamatergic neuroprotection in the hAβ1–42Glu;ApoE4 worms and other worm strains. Left: distribution of worms with different numbers of 5 designated tail neurons (n = 80–100 from 2 biological replicates). Right: the fluorescent intensity of PVR neurons (n = 15 from 2 biological replicates). e, Effects of Kaem and Rhap on acetylcholinesterase inhibitor aldicarb-induced paralysis. VC223 (a strain hypersensitive to aldicarb-induced paralysis) and NM204 (a strain resistant to aldicarb-induced paralysis) were used as controls. All quantitative data are shown as mean ± s.e.m. Two-way ANOVA followed by Tukey’s multiple comparisons test (a–e); NS, no significance; *P < 0.05, **P < 0.01, ***P < 0.001. Effects of Kaem and Rhap on Aβ generation in mouse neuroblastoma cells are shown in Extended Data Fig. 1c–f. Additional data related to e are in Supplementary Fig. 6.
