β-Amyloid (Aβ) oligomers are neurotoxic and implicated in Alzheimer's disease. Neuronal plasma membranes may mediate formation of Aβ oligomers in vivo. Membrane components sphingomyelin and GM1 have been shown to promote aggregation of Aβ; however, these studies were performed under extreme, non-physiological conditions. We demonstrate that physiological levels of GM1 , organized in nanodomains do not seed oligomerization of Aβ40 monomers. We show that sphingomyelin triggers oligomerization of Aβ40 and that GM1 is counteractive thus preventing oligomerization. We propose a molecular explanation that is supported by all-atom molecular dynamics simulations. The preventive role of GM1 in the oligomerization of Aβ40 suggests that decreasing levels of GM1 in the brain, for example, due to aging, could reduce protection against Aβ oligomerization and contribute to the onset of Alzheimer's disease.

Faculty of Science and CEITEC Masaryk University Brno Czech Republic

J Heyrovský Inst Physical Chemistry of the A S C R v v i Prague Czech Republic

Shemyakin Ovchinnikov Inst Bioorganic Chemistry of the R A S Moscow GSP 7 Russian Fed

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Bucciantini M., Giannoni E., Chiti F., Baroni F., Formigli L., Zurdo J., Taddei N., Ramponi G., Dobson C. M., Stefani M., Nature 2002, 416, 507–511; PubMed

Shankar G. M., Li S., Mehta T. H., Garcia-munoz A., Nina E., Smith I., Brett F. M., Farrell M. A., Rowan M. J., Lemere C. A. et al., Nat. Med. 2008, 1 4, 837–842. PubMed PMC

Amaro M., Birch D. J. S., Rolinski O. J., Phys. Chem. Chem. Phys. 2011, 13, 6434–6441; PubMed

Narayan P., Orte A., Clarke R. W., Bolognesi B., Hook S., Ganzinger K. A., Meehan S., Wilson M. R., Dobson C. M., Klenerman D., Nat. Struct. Mol. Biol. 2011, 19, 79–83. PubMed PMC

de Almeida R. F. M., Fedorov A., Prieto M., Biophys. J. 2003, 85, 2406–2416. PubMed PMC

Devanathan S., Salamon Z., Lindblom G., Gröbner G., Tollin G., FEBS J. 2006, 273, 1389–1402; PubMed

Chi E. Y., Ege C., Winans A., Majewski J., Wu G., Kjaer K., Lee K. Y. C., Proteins Struct. Funct. Bioinf. 2008, 72, 1–24; PubMed

Williams T. L., Johnson B. R. G., Urbanc B., Jenkins A. T. A., Connell S. D. A., Serpell L. C., Biochem. J. 2011, 439, 67–77. PubMed

Yanagisawa K., J. Neurochem. 2011, 116, 806–812. PubMed

Ledeen R. W., J. Supramol. Struct. 1978, 8, 1–17. PubMed

Tettamanti G., Anastasia L. in Handb. Neurochem. Mol. Neurobiol. (Eds.: A. Lajtha, G. Tettamanti, G. Goracci), Springer, Boston, 2010, pp. 99–171.

Ariga T., McDonald M. P., Yu R. K., J. Lipid Res. 2008, 49, 1157–1175; PubMed PMC

Mocchetti I., Cell. Mol. Life Sci. 2005, 62, 2283–2294. PubMed PMC

Kreutz F., Frozza R. L., Breier A. C., Oliveira V. A., Horn A. P., Pettenuzzo L. F., Netto C. A., Salbego C. G., Trindade V. M. T., Neurochem. Int. 2011, 59, 648–655; PubMed

Yang R., Wang Q., Min L., Sui R., Li J., Liu X., Neurol. Sci. 2013, 34, 1447–1451; PubMed

Kreutz F., Scherer E. B., Ferreira A. G. K., Petry F. D. S., Pereira C. L., Santana F., de Souza Wyse A. T., Salbego C. G., Trindade V. M. T., Neurochem. Res. 2013, 38, 2342–2350. PubMed

Göttfert F., Wurm C. A., Mueller V., Berning S., Cordes V. C., Honigmann A., Hell S. W., Biophys. J. 2013, 105, L01–L03; PubMed PMC

Sevcsik E., Schütz G. J., BioEssays 2016, 38, 129–139. PubMed PMC

Macháň R., Hof M., Biochim. Biophys. Acta Biomembr. 2010, 1798, 1377–1391. PubMed

Sachl R., Amaro M., Aydogan G., Koukalová A., Mikhalyov I. I., Boldyrev I. A., Humpolíčková J., Hof M., Biochim. Biophys. Acta Mol. Cell Res. 2015, 1853, 850–857. PubMed

Amaro M., Sachl R., Jurkiewicz P., Coutinho A., Prieto M., Hof M., Biophys. J. 2014, 107, 2751–2760. PubMed PMC

Cohen S. I. A., Vendruscolo M., Welland M. E., Dobson C. M., Terentjev E. M., Knowles T. P. J., J. Chem. Phys. 2011, 135, 065105. PubMed PMC

Kakio A., Nishimoto S. I., Yanagisawa K., Kozutsumi Y., Matsuzaki K., J. Biol. Chem. 2001, 276, 24985–24990; PubMed

Kakio A., Nishimoto S., Yanagisawa K., Kozutsumi Y., Matsuzaki K., Biochemistry 2002, 41, 7385–7390. PubMed

Sagle L. B., Ruvuna L. K., Bingham J. M., Liu C., Cremer P. S., Van Duyne R. P., J. Am. Chem. Soc. 2012, 134, 15832–15839. PubMed PMC

Devarajan S., Sharmila J. S., J. Mol. Liq. 2014, 195, 59–64;

Manna M., Mukhopadhyay C., PLoS One 2013, 8, e71308. PubMed PMC

Vácha R., Linse S., Lund M., J. Am. Chem. Soc. 2014, 136, 11776–11782; PubMed

Minton A. P., Biophys. Chem. 2000, 86, 239–247; PubMed

Minton A. P., Biophys. J. 2001, 80, 1641–1648. PubMed PMC

Kracun I., Rosner H., Drnovsek V., Vukelic Z., Cosovic C., Trbojevic-Cepe M., Kubat M., Neurochem. Int. 1992, 20, 421–431. PubMed

Sokolova T. V., Zakharova I. O., Furaev V. V., Rychkova M. P., Avrova N. F., Neurochem. Res. 2007, 32, 1302–1313. PubMed

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