Amyloid β Binds to Albumin-Associated Lrp-Like Plasma O-Glycoproteins: Albumin Prevents Inhibition of Binding by LDL

Author(s): Sreedevi Karthi, K. C. Sumitha, Mandagini Geetha, Padinjaradath S. Appukuttan*

Journal Name: Protein & Peptide Letters

Volume 26 , Issue 11 , 2019


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Graphical Abstract:


Abstract:

Background: Albumin was reported to engage nearly 95% of plasma Amyloid β (Aβ) and to reverse Aβ fibril formation in brain.

Objective: Since O-glycosylated LRP family of receptors capture Aβ in brain we compared Aβ binding to electrophoretically purified albumin and to O-glycoproteins AOP1 and AOP2 that adhere noncovalently to plasma albumin.

Methods: Strength of Aβ-protein interaction was measured as fluorescence increase in Fluorescentlabeled Aβ (F-Aβ) resulting from conformational changes. Alternatively, differential segregation of free and protein-bound Aβ in Density Gradient Ultracentrifugation (DGUC) was also examined.

Results: Fluorescence enhancement in F-Aβ was significantly greater by AOP1 and AOP2 than by known Aβ reactants α -synuclein and β -cyclodextrin, but nil by albumin. In DGUC Aβ migrated with the O-glycoproteins but not with albumin. Free O-glycoproteins unlike their albumin-bound forms were blocked by LDL from capturing F-Aβ. Associated albumin did not affect Aβ binding of O-glycoproteins. De-O-glycosylation of AOP1/AOP2 enhanced their Aβ binding showing that peptide sequences at O-glycosylated regions were recognized by Aβ. Unlike albumin, AOP1 and AOP2 were immunologically cross-reactive with LRP. Albumin sample used earlier to report albumin-Aβ interaction contained two O-glycoproteins cross-reactive with human LRP and equal in size to human AOP1 or AOP2.

Conclusion: Unlike albumin, albumin-bound O-glycoproteins, immunologically cross-reactive with LRP, bind plasma Aβ. These O-glycoproteins are potential anti-amyloidogenic therapeutics if they inhibit Aβ aggregation as other Aβ reactants do. Circulating immune complexes of albuminbound O-glycoproteins with O-glycoprotein-specific natural antibodies can bind further to LRP-like membrane proteins and are possible O-glycoprotein transporters to tissues.

Keywords: Anti-α-galactoside antibody, anti-β-glucoside antibody, albumin-associated-O-glycosylated protein, amyloid β, serine- and threonine-rich peptide sequence, LRP.

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Article Details

VOLUME: 26
ISSUE: 11
Year: 2019
Published on: 23 October, 2019
Page: [869 - 878]
Pages: 10
DOI: 10.2174/0929866526666190722151027
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