Figure 2.

LAMP2A prevents SNCA-induced behavioral and oxidative defects in Drosophila. (a) LAMP2A coexpression fully prevented the progressive locomotor defects induced by pan-neuronal SNCA^A30P. Climbing ability (SING assay) of elav>LAMP2A, SNCA^A30P flies was compared to that of elav>SNCA^A30P and elav>LAMP2A flies at 10, 31 and 38 days after a.E. (b) Human LAMP2A reduced neuronal SNCA accumulation. Western blots of head protein extracts from 30-day-old elav>SNCA^A30P flies compared to elav>LAMP2A, SNCA^A30P probed with anti-SNCA antibody. Act5C was used as a loading control. Quantification of SNCA^A30P protein level from 3 independent experiments. Coexpression of LAMP2A reduced SNCA^A30P accumulation without decreasing its mRNA level (see Fig. S2A). (c) ROS levels in the brain of elav>LAMP2A, SNCA^A30P flies were lower than those of elav>SNCA^A30Pand comparable to the elav/+ control at both 2 and 30 days a.E. Representative pictures of DHE-labeled brains are shown in Figure S2B. (d) MDA concentration assayed in the brain of 2- and 30-day-old adult Drosophila as an index of lipid peroxidation. Brain MDA level was markedly increased in elav>SNCA^A30P flies but not in elav>LAMP2A, SNCA^A30P flies that show similar levels as the elav/+ control.