Fig. 3.
Blocking RAGE or genetic deletion of the receptor suppresses Aβ uptake and minimizes Aβ-induced mitochondrial dysfunction in cortical neurons. Intracellular levels of human Aβ1–40 (A and B) and COX IV activity (C–F) were assayed 60 min (A and B) and 24 h (C–F) after exposure to the indicated Aβ peptides. (A) Effect of a neutralizing antibody to RAGE. Cells were pre-treated with 20 μg/mL of anti-RAGE (N-16) IgG or NI-IgG for 2 h, and then exposed to 1 μM human Aβ1–40. (B, E, and F) Effect of genetic deletion of RAGE. Cells prepared from WT or RAGE−/− mice were exposed to the indicated concentrations of human Aβ1–40 (B and E) or Aβ1–42 (F). (C and D) Aβ-related peptides with the reverse sequence have no effect on mitochondrial function in cortical neurons. Cells prepared from wild-type mice were exposed to 1 μM human Aβ1–40 or Aβ40–1 (C), and 1 μM human Aβ1–42 or Aβ42–1 (D). Data represent mean ± SEM; **, P < 0.01, versus vehicle- and reversed Aβ-treated cells (A–D), or Aβ-treated RAGE−/− neurons (E and F); ††, P < 0.01, versus control (A and B) or WT (E and F).