Intervention into amyloid deposition with anti-amyloid agents like the polyphenol Epigallocatechin-3-gallate (EGCG) is emerging as an experimental secondary treatment strategy in systemic light chain amyloidosis (AL). In both AL and Multiple Myeloma (MM), soluble immunoglobulin light chains (LC) are produced by clonal plasma cells, but only in AL they form amyloid deposits in vivo. We investigated the amyloid formation of patient-derived LC and their susceptibility to EGCG in vitro to probe commonalities and systematic differences in their assembly mechanisms. We isolated nine LC from urine of AL and MM patients. We quantified their thermodynamic stabilities, and monitored their aggregation under physiological conditions by ThT fluorescence, light scattering, SDS-stability and atomic force microscopy. LC from all patients formed amyloid-like aggregates, albeit with individually different kinetics. LC existed as dimers, ~50% of which were linked by disulfide bridges. Our results suggest that cleavage into LC monomers is required for efficient amyloid formation. The kinetics of AL LC displayed a transition point in concentration dependence, which MM LC lacked. The lack of concentration dependence of MM LC aggregation kinetics suggests that conformational change of the light chain is rate-limiting for these proteins. Aggregation kinetics displayed two distinct phases, which corresponded to the formation of oligomers and amyloid fibrils, respectively. EGCG specifically inhibited the second aggregation phase and induced the formation of SDS-stable, non-amyloid LC aggregates. Our data suggest that EGCG intervention does not depend on the individual LC sequence and is similar to the mechanism observed for amyloid-β and α-synuclein.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2hybA74
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
-
Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
-
2016-11-22T07-55-59Z Source: International Journal of Medical Science and Public Health Banothu Srinivas, Madhu Mohan Reddy B. Backgrou...
-
2016-10-15T06-30-01Z Source: The Southeast Asian Journal of Case Report and Review Sangita Deepak Kamath, Neeraj Jain, Saurabh Pathak, Ba...
-
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with cl...
-
Abstract The development of focused ion beam-scanning electron microscopy (FIB-SEM) techniques has allowed high-resolution 3D imaging of n...
-
Vol.48 No.2 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1S2Z7n2 via IFTTT
-
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου