Single molecule experiments emphasize GM1 as a key player of the different cytotoxicity of structurally distinct A beta 1-42 oligomers
Authors: Calamai M., Evangelisti E., Cascella R., Parenti N., Cecchi C., Stefani M., Pavone F.
Autors Affiliation: Univ Florence, European Lab Nonlinear Spect LENS, I-50019 Florence, Italy; Natl Res Council Italy CNR, Natl Inst Opt, Largo Fermi 6, I-50125 Florence, Italy; Univ Florence, Dipartimento Sci Biomed Sperimentali & Clin Mario, I-50134 Florence, Italy; CIMN, I-50134 Florence, Italy
Abstract: It is well established that cytotoxic A beta oligomers are the key factor that triggers the initial tissue and cell modifications eventually culminating in the development of Alzheimer’s disease. A beta 1-42 oligomers display a high degree of polymorphism, and several structurally different oligomers have been described. Amongst them, two types, recently classified as A+ and A-, have been shown to possess similar size but distinct toxic properties, as a consequence of their biophysical and structural differences. Here, we have investigated by means of single molecule tracking the oligomer mobility on the plasma membrane of living neuroblastoma cells and the interaction with the ganglioside GM1, a component of membrane rafts. We have found that A+ and A- oligomers display a similar lateral diffusion on the plasma membrane of living cells. However, only the toxic A+ oligomers appear to interact and alter the mobility of GM1. We have also studied the lateral diffusion of each kind of oligomers in cells depleted or enriched in GM1. We found that the content of GM1 influences the diffusion of both types of oligomer, although the effect of the increased levels of GM1 is higher for the A+ type. Interestingly, the content of GM1 also affects significantly the mobility of GM1 molecules themselves. (C) 2015 Elsevier B.V. All rights reserved.
Journal/Review: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume: 1858 (2) Pages from: 386 to: 392
KeyWords: GM1 ganglioside; Single molecule tracking; A beta oligomers; Alzheimer’s diseaseDOI: 10.1016/j.bbamem.2015.12.009Citations: 16data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2021-10-24References taken from IsiWeb of Knowledge: (subscribers only)Connecting to view paper tab on IsiWeb: Click hereConnecting to view citations from IsiWeb: Click here