Modulation of pTau181 by Glypican-1-Derived Heparan Sulfate in Human Neural Progenitor Cells and ApoE4-Expressing Induced Neurons.

ABSTRACT: In Alzheimer's disease (AD) there is accumulation of amyloid-β (Aβ) and hyperphosphorylated tau (pTau) in the brain. Aβ activates kinases that phosphorylate tau. Increased pTau181 is a signal for hyperphosphorylation of tau. The generation of Aβ from amyloid precursor protein (APP) and the release of heparan sulfate (HS) from the proteoglycan glypican-1 (GPC1) are interconnected. Release of HS is APP-, ascorbate-, copper-, and NO-dependent. HS-Aβ interactions may regulate tau phosphorylation in human neural stem cells (NSC). The most influential risk factor for sporadic AD is the presence of the ε4 allele of apolipoprotein E (ApoE). Here, we have further explored the interplay between GPC1-derived HS and pTau181 formation in human neural progenitor cells (NPC) and induced neurons (iN) obta

SUBMITTER: Cheng F 

PROVIDER: S-EPMC12269345 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature