Abeta42-Induced Neurodegeneration via an Age-Dependent Autophagic-Lysosomal Injury in Drosophila (original) (raw)
Figure 8
Autophagy activity affects Aβ1–42 neurotoxicity.
(A) Drosophila incorporating a heterozygous loss-of-function allele Atg1Δ3D (Atg1+/−) exhibit a significant decrease in expression levels of Atg1 mRNA in fly brains (data are normalized mean+SEM relative to GAPDH, two-tailed P values by Student's t-test, n = 3 for each group). (B) Control flies with Atg1+/− genotype have a shortened mean lifespan compared to Atg1+/+ genotype (−13.6%, log-rank P<0.0001). In contrast, Aβ1–42 flies with Atg1+/− genotype have extended lifespan relative to Atg1+/+ genotype (+10.9%, log-rank P<0.0001) (data are the mean±SEM). (C) Normalized expression levels of Aβ1–42 transcripts exhibit no significant difference in Aβ1–42 fly heads between Atg1+/+ and Atg1+/− genotypes (data are the mean+SEM, N = 3 for each group, two-tailed P value by student's t test). (D) Aβ1–42 flies with Atg1+/− genotype have significantly fewer fluorescent puncta in targeted neurons relative to Atg1+/+ genotype (fly age is 11 days, data are the mean+SEM, two-tailed P value by Student's t-test, n = 9 for each group). (E) Autophagy activation by rapamycin feeding (1 µM) results in a shorter lifespan for Aβ1–42 flies (−26.0%, log-rank P<0.0001), but has no obvious effect on the lifespan of Aβ1–40 flies (−1.5%, log-rank P = 0.076) relative to flies fed with the same amount of DMSO (data are the mean±SEM). N is the sample size of fly cohorts for each experimental condition.