Alpha 2-macroglobulin synthesis in interleukin-6-stimulated human neuronal (SH-SY5Y neuroblastoma) cells. Potential significance for the processing of Alzheimer beta-amyloid precursor protein.
Cultured human neuronal (SH-SY5Y neuroblastoma) cells synthesize and secrete the potent protease inhibitor alpha 2-macroglobulin (a2M) upon stimulation with interleukin-6 (IL-6) indicating that alpha 2-macroglobulin behaves as an acute-phase protein in the human central nervous system. Exogenous addition of a2M to the cultured neuronal cells resulted in only a slight inhibition of Alzheimer beta A4-amyloid precursor protein (APP) synthesis, but markedly inhibited its secretion pointing to the possibility that a2M may affect the proteolytic APP processing. Evidence is provided that IL-6 and a2M are involved in Alzheimer's disease pathogenesis.
Ganter
U
U
Psychiatrische Universitätsklinik, Universität Freiburg, Germany.
Strauss
S
S
Jonas
U
U
Weidemann
A
A
Beyreuther
K
K
Volk
B
B
Berger
M
M
Bauer
J
J
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D011233:Precipitin Tests; D011480:Protease Inhibitors; D011498:Protein Precursors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000511:alpha-Macroglobulins / Q000096:biosynthesis*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015850:Interleukin-6; D011480:Protease Inhibitors; D011498:Protein Precursors; D000511:alpha-Macroglobulins