PMID- 8163522 OWN - NLM STAT- MEDLINE DCOM- 19940526 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 269 IP - 16 DP - 1994 Apr 22 TI - Increased amyloid production from aberrant beta-amyloid precursor proteins. PG - 12179-84 AB - 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. FAU - Zhong, Z AU - Zhong Z AD - Scios Nova Inc., Mountain View, California 94043. FAU - Quon, D AU - Quon D FAU - Higgins, L S AU - Higgins LS FAU - Higaki, J AU - Higaki J FAU - Cordell, B AU - Cordell B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Recombinant Proteins) RN - 0 (Sulfur Radioisotopes) RN - AE28F7PNPL (Methionine) RN - K848JZ4886 (Cysteine) SB - IM MH - Amyloid beta-Peptides/*biosynthesis/isolation & purification MH - Amyloid beta-Protein Precursor/*biosynthesis/isolation & purification/metabolism MH - Animals MH - Cell Line MH - Chlorocebus aethiops MH - Cysteine/metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Humans MH - Kinetics MH - Methionine/metabolism MH - Models, Biological MH - Molecular Weight MH - Neuroblastoma MH - *Protein Processing, Post-Translational MH - Recombinant Proteins/biosynthesis/isolation & purification/metabolism MH - Sulfur Radioisotopes MH - Tumor Cells, Cultured EDAT- 1994/04/22 00:00 MHDA- 1994/04/22 00:01 CRDT- 1994/04/22 00:00 PHST- 1994/04/22 00:00 [pubmed] PHST- 1994/04/22 00:01 [medline] PHST- 1994/04/22 00:00 [entrez] AID - S0021-9258(17)32698-4 [pii] PST - ppublish SO - J Biol Chem. 1994 Apr 22;269(16):12179-84.