Increased amyloid production from aberrant beta-amyloid precursor proteins.
The 4-kDa beta-amyloid protein that forms fibrillar deposits in Alzheimer's diseased brains is derived from a large precursor, the beta-amyloid precursor protein (beta-APP). Recently, it has been reported that beta-amyloid is normally produced and secreted by cultured mammalian cells. In our studies involving recombinant expression of beta-APP, increased yields of beta-amyloid were associated with expression of aberrant beta-APP molecules. Deletion mutations within the beta-amyloid domain, incorrect beta-APP isoform expression in fibroblasts or neuronal cells, or excess amounts of beta-APP all led to increases in beta-amyloid production. Aberrant beta-APP appears to be diverted from the secretory pathway and then degraded to beta-amyloid.
Zhong
Z
Z
Scios Nova Inc., Mountain View, California 94043.
Quon
D
D
Higgins
L S
LS
Higaki
J
J
Cordell
B
B
D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000302:isolation & purification; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008954:Models, Biological; D008970:Molecular Weight; D009447:Neuroblastoma; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D008715:Methionine; D003545:Cysteine