Phosphorylation and Glycosylation of Amyloid-β Protein Precursor: The Relationship to Trafficking and Cleavage in Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder in the central nervous system, and this disease is characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid-beta (A beta) peptide is the main constituent of senile plaques, and this peptide is derived from the amyloid-beta protein precursor (A beta PP) through the successive cleaving by beta-site A beta PP-cleavage enzyme 1 (BACE1) and beta-secretase. A beta PP undergoes the progress of post-translational modifications, such as phosphorylation and glycosylation, which might affect the trafficking and the cleavage of A beta PP. In the recent years, about 10 phosphorylation sites of A beta PP were identified, and they play complex roles in glycosylation modification and cleavage of A beta PP. In this article, we introduced the transport and the cleavage pathways of A beta PP, then summarized the phosphorylation and glycosylation sites of A beta PP, and further discussed the links and relationship between phosphorylation and glycosylation on the pathways of A beta PP trafficking and cleavage in order to provide theoretical basis for AD research.

Automated summary

Alzheimer's disease is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles. The main constituent of senile plaques, Aβ peptide, is derived from AβPP through cleaving by enzymes. Post-translational modifications like phosphorylation and glycosylation of AβPP may affect its trafficking and cleavage.