Expression of B4GALNT1, an essential glycosyltransferase for the synthesis of complex gangliosides, suppresses BACE1 degradation and modulates APP processing.

ABSTRACT: Alzheimer's disease (AD) is the most prevalent form of dementia characterized by the extracellular accumulation of amyloid β (Aβ) peptides, which are produced by proteolytic cleavages of amyloid precursor protein (APP). Gangliosides are involved in AD pathophysiology including Aβ deposition and APP processing, yet the detailed mechanisms are not fully understood. Here we examined how changes in the carbohydrate moiety of gangliosides alter APP processing in human melanoma cells, neuroectoderm-derived cells. We showed that forced expression of GD2, GM2 or GM1 (by introducing B4GALNT1 cDNA into cells not expressing this glycosyltransferase) results in increases of α- and β-site cleavages of APP with a prominent increase in β-cleavage. We also showed that β-site APP cleaving enzyme 1 (BACE1)

SUBMITTER: Yamaguchi T 

PROVIDER: S-EPMC5043288 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature