Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes.

ABSTRACT: Accumulation of amyloid-β peptides (Aβ) in the brain is a common pathological feature of Alzheimer disease (AD). Aggregates of Aβ are neurotoxic and appear to be critically involved in the neurodegeneration during AD pathogenesis. Accumulation of Aβ could be caused by increased production, as indicated by several mutations in the amyloid precursor protein or the γ-secretase components presenilin-1 and presenilin-2 that cause familial early-onset AD. However, recent data also indicate a decreased clearance rate of Aβ in AD brains. We recently demonstrated that Aβ undergoes phosphorylation by extracellular or cell surface-localized protein kinase A, leading to increased aggregation. Here, we provide evidence that phosphorylation of monomeric Aβ at Ser-8 also decreases its clearance by microg

SUBMITTER: Kumar S 

PROVIDER: S-EPMC3318721 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature