Home
Resources
Publications
Generation and Regulation of Beta-Amyloid Peptide Variants by Neurons

Generation and Regulation of Beta-Amyloid Peptide Variants by Neurons

G K Gouras, H Xu, J N Jovanovic, J D Buxbaum, R Wang, P Greengard, N R Relkin, S Gandy

J Neurochem. 1998 Nov;71(5):1920-5.

PMID: 9798916

Abstract:

Studies of processing of the Alzheimer beta-amyloid precursor protein (betaAPP) have been performed to date mostly in continuous cell lines and indicate the existence of two principal metabolic pathways: the "beta-secretase" pathway, which generates beta-amyloid (A beta(1-40/42); approximately 4 kDa), and the "alpha-secretase" pathway, which generates a smaller fragment, the "p3" peptide (A beta(17-40/42); approximately 3 kDa). To determine whether similar processing events underlie betaAPP metabolism in neurons, media were examined following conditioning by primary neuronal cultures derived from embryonic day 17 rats. Immunoprecipitates of conditioned media derived from [35S]methionine pulse-labeled primary neuronal cultures contained 4- and 3-kDa A beta-related species. Radiosequencing analysis revealed that the 4-kDa band corresponded to conventional A beta beginning at position A beta(Asp1), whereas both radiosequencing and immunoprecipitation-mass spectrometry analyses indicated that the 3-kDa species in these conditioned media began with A beta(Glu11) at the N terminus, rather than A beta(Leu17) as does the conventional p3 peptide. Either activation of protein kinase C or inhibition of protein phosphatase 1/2A increased soluble betaAPP(alpha) release and decreased generation of both the 4-kDa A beta and the 3-kDa N-truncated A beta. Unlike results obtained with continuously cultured cells, protein phosphatase 1/2A inhibitors were more potent at reducing A beta secretion by neurons than were protein kinase C activators. These data indicate that rodent neurons generate abundant A beta variant peptides and emphasize the role of protein phosphatases in modulating neuronal A beta generation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248075	Amyloid β-Protein Fragment 17-40			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: