Phosphorylation of a full length amyloid-β peptide modulates its amyloid aggregation, cell binding and neurotoxic properties

Molecular BioSystems
Elaheh JamasbiGiuseppe D Ciccotosto


Amyloid beta peptide (Aβ) is the major protein component of the amyloid plaques that are present in the brains of Alzheimer's disease (AD) patients. Aβ42 peptide is a known neurotoxic agent that binds to neurons and, under specific aggregation conditions, triggers cell death. Aβ peptide can undergo specific amino acid posttranslational modifications, such as phosphorylation, that are important for modulating its proteolytic degradation, aggregation, binding to lipid membranes and neurotoxic functions. Peptides phosphorylated at serine 8 in full-length Aβ42 (pAβ42) were synthesised and compared to native Aβ42 peptide. Their secondary structures, aggregation properties and interactions with plasma membranes of primary cortical neurons were investigated. The results revealed that pAβ42 has increased β-sheet formation with rapid amyloid formation in a synthetic lipid environment, which was associated with increased cellular binding but concomitant diminished neurotoxicity. Our data support the notion that phosphorylation of Aβ42 promotes the formation of amyloid plaques in the brain, which lack the neurotoxic properties associated with oligomeric species causing pathogenesis in AD.


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Nov 27, 2015·Journal of Neurochemistry·Metta K JanaGiuseppe D Ciccotosto
Jun 3, 2016·The Journal of Biological Chemistry·Nasrollah Rezaei-GhalehMarkus Zweckstetter

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Apr 6, 2021·Journal of Alzheimer's Disease : JAD·Makoto HashimotoEliezer Masliah
Jun 23, 2021·Biochemical Society Transactions·Sunnia RajputFrances Separovic
Jun 28, 2021·Current Opinion in Chemical Biology·Stuart P MoonMatthew R Pratt

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