Phosphorylation at Ser 8 as an Intrinsic Regulatory Switch to Regulate the Morphologies and Structures of Alzheimer's 40-residue {beta}-Amyloid (A{beta}40) Fibrils [Protein Structure and Folding]

Polymorphism of amyloid-β (Aβ) fibrils, implying different fibril structures, may play important pathological roles in Alzheimer's disease (AD). Morphologies of Aβ fibrils were found to be sensitive to fibrillation conditions. Herein, the Ser-8-phosphorylated Aβ (pAβ), which is assumed to specially associate with symptomatic AD, is reported to modify the morphology, biophysical properties, cellular toxicity and structures of Aβ fibrils. Under the same fibrillation conditions, the pAβ favors the formation of different fibrils (Fpβ) from that of wild-type Aβ (Fβ). Both Fβ and Fpβ fibrils show single predominant morphologies. Compared with Fβ, Fpβ exhibits higher propagation efficiency and higher neuronal cell toxicity. The residue-specific structural differences between the Fβ- and Fpβ-seeded Aβ fibrils are identified using Magic Angle Spin (MAS) NMR. Our results suggest a potential regulatory mechanism of phosphorylation on Aβ fibril formation in AD, and imply that the post-translational modified Aβ, especially the phosphorylated Aβ may be an important target to diagnose or cure AD at specific stages.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hy45Nq
via IFTTT