Research Paper Advance Articles

Nmnat2 attenuates amyloidogenesis and up-regulates ADAM10 in AMPK activity-dependent manner

Decrease of ADAM10 is simultaneous with the increase of Aβ productions in the cortex of 10-month old Tg2576 mice. (A) The scheme of the proteolytic processing of APP. Aβ, amyloid-β peptide with 40 (Aβ1-40), or 42 amino acid residues (Aβ1-42); APP, amyloid precursor protein; AICD, APP intracellular domain; APPα, soluble APP after α-secretase cleavage (α-fragment); APPβ, soluble APP after β-secretase cleavage; C99, C-terminal fragment of APP of 99 amino acids after β-secretase cleavage (β-CTF); C83, C-terminal fragment of APP of 83 amino acids after α-secretase cleavage (α-CTF); P3, N-terminal fragment of C83 after α-secretase cleavage. (B–F) The cortex extracts were prepared from 10 months old Tg2576 mice (Tg) and the age-matched littermates (Non-Tg), then the levels of ADAM10, α-CTF, and Aβ productions were measured by western blot (B, D, E) and quantitative analysis (C, F) (n=5 for each group). The data were expressed as means ± S.D. *P P

Figure 1. Decrease of ADAM10 is simultaneous with the increase of Aβ productions in the cortex of 10-month old Tg2576 mice. (A) The scheme of the proteolytic processing of APP. Aβ, amyloid-β peptide with 40 (Aβ1-40), or 42 amino acid residues (Aβ1-42); APP, amyloid precursor protein; AICD, APP intracellular domain; APPα, soluble APP after α-secretase cleavage (α-fragment); APPβ, soluble APP after β-secretase cleavage; C99, C-terminal fragment of APP of 99 amino acids after β-secretase cleavage (β-CTF); C83, C-terminal fragment of APP of 83 amino acids after α-secretase cleavage (α-CTF); P3, N-terminal fragment of C83 after α-secretase cleavage. (BF) The cortex extracts were prepared from 10 months old Tg2576 mice (Tg) and the age-matched littermates (Non-Tg), then the levels of ADAM10, α-CTF, and Aβ productions were measured by western blot (B, D, E) and quantitative analysis (C, F) (n=5 for each group). The data were expressed as means ± S.D. *P < 0.05, **P < 0.01 vs control.