MT5‐MMP controls APP and β‐CTF/C99 metabolism through proteolytic‐dependent and ‐independent mechanisms relevant for Alzheimer's disease

authors

• García‐gonzález Laura
• Paumier Jean‐michel
• Louis Laurence
• Pilat Dominika
• Bernard Anne
• Stephan Delphine
• Jullien Nicolas
• Checler Frédéric
• Nivet Emmanuel
• Khrestchatisky Michel
• Baranger Kévin
• Rivera Santiago

abstract

Abbreviations: 3xTG, transgenic mice expressing human APP, MAPT, and PSEN1 genes with three familial mutations; 5xFAD, transgenic mice expressing human APP and PSEN1 genes with five familial mutations; AD, Alzheimer's disease; ADAM, a disintegrin and metalloprotease; APP, amyloid protein precursor; Aβ, beta-amyloid peptide; BACE-1, beta-site APP-cleaving enzyme-1; C3, BACE-1 inhibitor IV; C99/C83, APP CTF of 99/83 amino acids; CAT-, deletion of the catalytic domain; CTF, C-terminal fragment; DAPT, γ-secretase inhibitor; EXT-, deletion of the extracellular domain; GFP, green fluorescent protein; HEKswe, human embryonic kidney cells carrying the APP Swedish mutation; HPX-, deletion of the hemopexin domain; HRP, horseradish peroxidase enzyme; IC-, deletion of the intracytoplasmic domain; MMP, matrix metalloproteinase; MT1/5-MMP, membrane-type 1/5 matrix metalloproteinase; MT1/5Δ-MMP, catalytically inactive MT1-MMP or MT5-MMP; MTT, 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide; PSEN 1(2), presenilin 1 and 2; qPCR, quantitative polymerase chain reaction; RFP, red fluorescent protein; RXP03, MMP inhibitor; sAPP95, soluble amyloid protein precursor fragment generated by MT5-MMP; sAPPFL, full-length soluble amyloid protein precursor; sAPPα/β, soluble APPα/β; Tf, transferrin; TIMP, tissue inhibitor of MMPs; TIMP-1Δ, inactive TIMP-1; TM/IC-, deletion of the transmembrane and intracytoplasmic domains.

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