Mucin-Type O-Glycosylation Proximal to β-Secretase Cleavage Site Affects APP Processing and Aggregation Fate.

ABSTRACT: The amyloid-β precursor protein (APP) undergoes proteolysis by β- and γ-secretases to form amyloid-β peptides (Aβ), which is a hallmark of Alzheimer's disease (AD). Recent findings suggest a possible role of O-glycosylation on APP's proteolytic processing and subsequent fate for AD-related pathology. We have previously reported that Tyr⁶⁸¹-O-glycosylation and the Swedish mutation accelerate cleavage of APP model glycopeptides by β-secretase (amyloidogenic pathway) more than α-secretase (non-amyloidogenic pathway). Therefore, to further our studies, we have synthesized additional native and Swedish-mutated (glyco)peptides with O-GalNAc moiety on Thr⁶⁶³ and/or Ser⁶⁶⁷ to explore the role of glycosylation on conformation, secretase activity

SUBMITTER: Singh Y 

PROVIDER: S-EPMC9023740 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature