Hsp70 protected against iAβ toxicity by increasing proteasomal activity. Hsp70 protected against iAβ toxicity by increasing proteasomal activity. A–C, Recombinant Hsp70 was comicroinjected into neurons with p53 wild-type or dominant-negative constructs (A), recombinant Bax, Bcl2 (B), or caspase-6 (C) at 24 h (200 cells were injected for each treatment in each experiment, and every experiment was repeated 3 times). D, Hsp70 itself protected against iAβ1–42 toxicity at 24 h (200 cells were injected for each treatment in each experiment, and every experiment was repeated 3 times). **p < 0.01 compared with the iAβ1–42 groups. E, Proteasome inhibitor MG-132 blocked Hsp70 protection at 24 h (200 cells were injected for each treatment in each experiment, and every experiment was repeated 3 times). **p < 0.01, compared with iAβ1–42 + Hsp70 groups. F, Ub-EGFP was used as an indicator for proteasomal activity at 24 h. G, Hsp70 rescued proteasomal activity impaired by iAβ1–42 at 24 h. H, Quantification of Aβ degradation associated with ubiquitin by number of EGFP-positive cells over DTR-positive cells (200 cells were injected for each treatment in each experiment, and every experiment was repeated 3 times). **p < 0.01 compared with the iAβ1–42 groups. Data are presented as mean ± SE. I, Schematic drawing of morphine protection pathway. Morphine, EM-1, or EM-2 induced estrogen release by neurons and upregulation of ER through binding to their receptor MOR on cell membrane. Activated ER then induced increase of Hsp70, which rescued proteasomal activity impaired by iAβ. Jia Cui et al. J. Neurosci. 2011;31:16227-16240 ©2011 by Society for Neuroscience