MEK inhibitors suppress β‐amyloid production by altering the level of a β‐C‐terminal fragment of amyloid precursor protein in neuronal cells
Copyright policy )MEK inhibitors suppress β‐amyloid production by altering the level of a β‐C‐terminal fragment of amyloid precursor protein in neuronal cells
β‐Amyloid peptide (Aβ) is generated via sequential proteolysis of amyloid precursor protein (APP) by β‐ and γ‐secretases. Cell‐based screening experiments disclosed that the MEK (MAP kinase kinase) inhibitors, U0126 and PD184352, suppress Aβ secretion from human neuronal SH‐SY5Y cells expressing Swedish mutant APP. These inhibitors did not affect the cellular levels of APP but significantly reduced those of the APP β‐C‐terminal fragment (β‐CTF). Additionally, β‐CTF levels were markedly reduced by these inhibitors in cells expressing the fragment in a γ‐secretase‐independent and proteasome‐dependent manner. Our results suggest that MEK inhibitors reduce Aβ generation via secretase‐independent alteration of β‐CTF levels.
Mitogen-Activated Protein Kinase Kinases, Neurons, MEK inhibitor, Proteasome Endopeptidase Complex, Proteasome, Neuroblastoma, Amyloid beta-Protein Precursor, Amyloid precursor protein, Cell Line, Tumor, Benzamides, Nitriles, Butadienes, Humans, Amyloid Precursor Protein Secretases, β-Amyloid, Alzheimer’s disease, Protein Kinase Inhibitors, Signal Transduction
Mitogen-Activated Protein Kinase Kinases, Neurons, MEK inhibitor, Proteasome Endopeptidase Complex, Proteasome, Neuroblastoma, Amyloid beta-Protein Precursor, Amyloid precursor protein, Cell Line, Tumor, Benzamides, Nitriles, Butadienes, Humans, Amyloid Precursor Protein Secretases, β-Amyloid, Alzheimer’s disease, Protein Kinase Inhibitors, Signal Transduction
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