The ϐ-amyloid precursor protein (APP) plays a pivotal role in the early stages of neurodegeneration associated with Alzheimer's disease. An alteration in the processing pattern of the protein results in an increase in the generation of the 40-42-amino-acid ϐ-amyloid (Aϐ) peptide, which coalesces to form insoluble, extracellular amyloid deposits. A greater understanding of the factors that influence APP processing may assist in the design of effective therapeutic agents to halt progression of Alzheimer's disease. APP is a sialoglycoprotein with two potential N-linked glycosylation sites, one of which may contain a complex oligosaccharide chain. An alteration in the glycosylation state of APP by the generation of oligomannosyl oligosaccharides results in a decrease in the secretion of the neuroprotective, soluble form of the protein and a parallel increase in the deposition of the cellular protein within the perinuclear region of the cell. Conversely, the attachment of additional terminal sialic acid residues on to the oligosaccharide chain results in an increase in secretion of soluble APP (sAPPα). One factor that has been widely reported to alter APP processing is the activation of protein kinase C (PKC). This process has been characterized using synaptosomal preparations, which suggests that the PKC action is occurring at the level of the plasma membrane. Furthermore, when cells are transfected with the sialyltransferase enzyme, there is a direct relationship between the sialylation potential of APP and the fold stimulation of sAPPα, after PKC activation. These results suggest that the post-translational modification of APP by glycosylation is a key event in determining the processing of the protein.
Skip Nav Destination
Article navigation
February 2001
Issue Editors
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
Conference Article|
February 01 2001
The role of post-translational modification in ϐ-amyloid precursor protein processing
Niki Georgopoulou;
Niki Georgopoulou
1Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, U.K.
Search for other works by this author on:
Mark McLaughlin;
Mark McLaughlin
1Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, U.K.
Search for other works by this author on:
Ian McFarlane;
Ian McFarlane
1Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, U.K.
Search for other works by this author on:
Kieran C. Breen
Kieran C. Breen
1
1Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, U.K.
1To whom correspondence should be addressed.
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2001 The Biochemical Society
2001
Biochem Soc Symp (2001) 67: 23–36.
Citation
Cora O'Neill, Brian Anderton, Niki Georgopoulou, Mark McLaughlin, Ian McFarlane, Kieran C. Breen; The role of post-translational modification in ϐ-amyloid precursor protein processing. Biochem Soc Symp 1 February 2001; 67 23–36. doi: https://doi.org/10.1042/bss0670023
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Related Articles
Constitutive shedding of the amyloid precursor protein ectodomain is up-regulated by tumour necrosis factor-α converting enzyme
Biochem J (July,2001)
Glycosidase analysis of large acidic-type glycopeptides from viral and cellular membrane glycoproteins. Evidence for a common oligomannosyl core with branch sugar heterogeneity
Biochem J (March,1983)
Survival signalling in Alzheimer's disease
Biochem Soc Trans (October,2006)
Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer's disease
Biochem Soc Symp (February,2001)