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Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
The role of post-translational modification in beta-amyloid precursor protein processing
N Georgopoulou1, M McLaughlin, I McFarlane
1Department of Pharmacology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, U.K.
Biochemical Society Symposium
|July 13, 2001
Summary
Altering the glycosylation of beta-amyloid precursor protein (APP) impacts its processing. Increased sialic acid enhances neuroprotective soluble APP secretion, crucial for Alzheimer's disease research.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Alzheimer's disease involves beta-amyloid precursor protein (APP) processing.
- APP alterations increase beta-amyloid peptide generation, forming amyloid deposits.
- Understanding APP processing factors is key for therapeutic development.
Purpose of the Study:
- Investigate the role of APP glycosylation in its processing.
- Determine how altered glycosylation affects soluble APP (sAPP alpha) secretion and cellular deposition.
- Elucidate the link between protein kinase C (PKC) activation, sialylation, and APP processing.
Main Methods:
- Studied APP processing in synaptosomal preparations.
- Utilized cell transfection with sialyltransferase enzyme.
- Analyzed the relationship between APP sialylation and sAPP alpha secretion after PKC activation.
Main Results:
- Oligomannosyl oligosaccharides decrease soluble APP secretion and increase cellular deposition.
- Terminal sialic acid residues enhance soluble APP (sAPP alpha) secretion.
- PKC activation's effect on sAPP alpha secretion is directly related to APP sialylation potential.
Conclusions:
- Post-translational glycosylation of APP is a critical determinant of its processing pathway.
- Glycosylation state influences the balance between neuroprotective soluble forms and pathological deposits.
- Targeting APP glycosylation presents a potential therapeutic strategy for Alzheimer's disease.
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