Selective and Sensitive Pull Down of Amyloid Fibrils Produced in Vitro and in Vivo by the Use of Pentameric-Thiophene-Coupled Resins

ACS Chemical Neuroscience
Anna Beatriz WredenFernando L Palhano

Abstract

Protein aggregation is a hallmark of several degenerative diseases, including Alzheimer's disease, Parkinson's disease and familial amyloidosis (Finnish type) (FAF). A method to isolate and detect amyloids is desired for the diagnosis of amyloid diseases. Here, we report the synthesis of pentameric thiophene amyloid ligand (p-FTAA) linked to agarose resin for selective purification of amyloid aggregates produced in vitro and in vivo. Using amyloid fibrils produced in vitro from α-synuclein, gelsolin, and Aβ1-40 and gelsolin amyloid aggregates extracted from tissue homogenates of a mouse model of FAF, we observed that p-FTAA resin was able to pull down amyloid aggregates. The functionalized resin was also able to pull down oligomers produced in vitro from the A30P variant of α-synuclein. The methodology described here can be useful for the diagnosis of amyloidogenic disease and also can be used to purify amyloid fibrils from biological samples, rendering the fibrils available for more accurate structural and biochemical characterization.

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Citations

Dec 13, 2019·Seminars in Ophthalmology·Rosanna DammaccoFranco Dammacco
Nov 2, 2019·Chemical Reviews·Amir AliyanAngel A Martí

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