α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication

Scientific Reports

Volumn 7, Issue 1, 2017, Pages

  Aulić, Suzana ^a   Masperone, Lara ^a   Narkiewicz, Joanna ^a   Isopi, Elisa ^b   Bistaffa, Edoardo ^a,c   Ambrosetti, Elena ^d,e   Pastore, Beatrice ^a   De Cecco, Elena ^a   Scaini, Denis ^d,e   Zago, Paola ^a   Moda, Fabio ^c   Tagliavini, Fabrizio ^c   Legname, Giuseppe ^a,d  

^a SISSA   (Italy)

^b UNIVERSITY OF CHIETI   (Italy)

^c DEPARTMENT OF NEUROSURGERY   (Italy)

^d SINCROTRONE TRIESTE   (Italy)

^e UNIVERSITY OF TRIESTE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; AMYLOID; PRION PROTEIN; PRNP PROTEIN, MOUSE; PROTEIN BINDING; PROTEINASE K; RECOMBINANT PROTEIN; TYROSINE 3 MONOOXYGENASE;

ANIMAL; BRAIN; CHEMISTRY; CREUTZFELDT JAKOB DISEASE; GENE EXPRESSION REGULATION; GENETICS; HUMAN; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; KNOCKOUT MOUSE; METABOLISM; MOUSE; NERVE CELL; PATHOLOGY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; STEREOTACTIC PROCEDURE; TUMOR CELL LINE;

ALPHA-SYNUCLEIN; AMYLOID; ANIMALS; BRAIN; CELL LINE, TUMOR; CREUTZFELDT-JAKOB SYNDROME; ENDOPEPTIDASE K; GENE EXPRESSION REGULATION; HUMANS; INJECTIONS, INTRAVENTRICULAR; MICE; MICE, KNOCKOUT; NEURONS; PRION PROTEINS; PROTEIN BINDING; PROTEIN TRANSPORT; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; STEREOTAXIC TECHNIQUES; TYROSINE 3-MONOOXYGENASE;

EID: 85028526545     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-017-10236-x     Document Type: Article

References (44)

1. Lee, S. J., Desplats, P., Sigurdson, C., Tsigelny, I. & Masliah, E. Cell-to-cell transmission of non-prion protein aggregates. Nat Rev Neurol 6, 702-706, doi: 10.1038/nrneurol.2010.145 (2010).
2. McCann, H., Stevens, C. H., Cartwright, H. & Halliday, G. M. alpha-Synucleinopathy phenotypes. Parkinsonism Relat Disord 20(Suppl 1), S62-67, doi: 10.1016/s1353-8020(13)70017-8 (2014).
3. Li, J. Y. et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 14, 501-503, doi: 10.1038/nm1746 (2008).
4. Kordower, J. H., Chu, Y., Hauser, R. A., Freeman, T. B. & Olanow, C. W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 14, 504-506, doi: 10.1038/nm1747 (2008).
5. Desplats, P. et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA 106, 13010-13015, doi: 10.1073/pnas.0903691106 (2009).
6. Aulic, S. et al. Defined alpha-synuclein prion-like molecular assemblies spreading in cell culture. BMC Neurosci 15, 69, doi: 10.1186/1471-2202-15-69 (2014).
7. Luk, K. C. et al. Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice. J Exp Med 209, 975-986, doi: 10.1084/jem.20112457 (2012).
8. Luk, K. C. et al. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci USA 106, 20051-20056, doi: 10.1073/pnas.0908005106 (2009).
9. Luk, K. C. et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338, 949-953, doi: 10.1126/science.1227157 (2012).
10. Masuda-Suzukake, M. et al. Prion-like spreading of pathological alpha-synuclein in brain. Brain 136, 1128-1138, doi: 10.1093/brain/awt037 (2013).
11. Sung, J. Y. et al. Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein. J Biol Chem 276, 27441-27448, doi: 10.1074/jbc.M101318200 (2001).
12. Lee, H. J. et al. Assembly-dependent endocytosis and clearance of extracellular alpha-synuclein. Int J Biochem Cell Biol 40, 1835-1849, doi: 10.1016/j.biocel.2008.01.017 (2008).
13. Vella, L. J., Hill, A. F. & Cheng, L. Focus on Extracellular Vesicles: Exosomes and Their Role in Protein Trafficking and Biomarker Potential in Alzheimer's and Parkinson's Disease. Int J Mol Sci 17, doi: 10.3390/ijms17020173 (2016).
14. Emmanouilidou, E. et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 30, 6838-6851, doi: 10.1523/jneurosci.5699-09.2010 (2010).
15. Agnati, L. F. et al. A new hypothesis of pathogenesis based on the divorce between mitochondria and their host cells: possible relevance for Alzheimer's disease. Curr Alzheimer Res 7, 307-322 (2010).
16. Mao, X. et al. Pathological alpha-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science 353, doi: 10.1126/science.aah3374 (2016).
17. Westergard, L., Christensen, H. M. & Harris, D. A. The cellular prion protein (PrP(C)): its physiological function and role in disease. Biochim Biophys Acta 1772, 629-644, doi: 10.1016/j.bbadis.2007.02.011 (2007).
18. Lauren, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W. & Strittmatter, S. M. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457, 1128-1132, doi: 10.1038/nature07761 (2009).
19. Kessels, H. W., Nguyen, L. N., Nabavi, S. & Malinow, R. The prion protein as a receptor for amyloid-beta. Nature 466, E3-4, doi: 10.1038/nature09217 (2010). discussion E4-5.
20. Mehrabian, M. et al. CRISPR-Cas9-based knockout of the prion protein and its effect on the proteome. PLoS One 9, e114594, doi: 10.1371/journal.pone.0114594 (2014).
21. Nečas, D. & Klapetek, P. Gwyddion: an open-source software for SPM data analysis. Central European Journal of Physics 10, 181-188, doi: 10.2478/s11534-011-0096-2 (2011).
22. Butler, D. A. et al. Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins. J Virol 62, 1558-1564 (1988).
23. Bueler, H. et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356, 577-582, doi: 10.1038/356577a0 (1992).
24. Prusiner, S. B. et al. Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc Natl Acad Sci USA 90, 10608-10612 (1993).
25. Solforosi, L. et al. Toward molecular dissection of PrPC-PrPSc interactions. J Biol Chem 282, 7465-7471, doi: 10.1074/jbc.M610051200 (2007).
26. Resenberger, U. K. et al. The cellular prion protein mediates neurotoxic signalling of beta-sheet-rich conformers independent of prion replication. Embo j 30, 2057-2070, doi: 10.1038/emboj.2011.86 (2011).
27. Chen, S., Yadav, S. P. & Surewicz, W. K. Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues. J Biol Chem 285, 26377-26383, doi: 10.1074/jbc.M110.145516 (2010).
28. Fluharty, B. R. et al. An N-terminal fragment of the prion protein binds to amyloid-beta oligomers and inhibits their neurotoxicity in vivo. J Biol Chem 288, 7857-7866, doi: 10.1074/jbc.M112.423954 (2013).
29. Fujiwara, H. et al. alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4, 160-164, doi: 10.1038/ncb748 (2002).
30. Brandner, S. et al. Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379, 339-343, doi: 10.1038/379339a0 (1996).
31. Mallucci, G. et al. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 302, 871-874, doi: 10.1126/science.1090187 (2003).
32. Saborio, G. P., Permanne, B. & Soto, C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 411, 810-813, doi: 10.1038/35081095 (2001).
33. Morales, R., Duran-Aniotz, C., Diaz-Espinoza, R., Camacho, M. V. & Soto, C. Protein misfolding cyclic amplification of infectious prions. Nat Protoc 7, 1397-1409, doi: 10.1038/nprot.2012.067 (2012).
34. Colby, D. W. et al. Prion detection by an amyloid seeding assay. Proc Natl Acad Sci USA 104, 20914-20919, doi: 10.1073/pnas.0710152105 (2007).
35. Mougenot, A. L. et al. Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging 33, 2225-2228, doi: 10.1016/j.neurobiolaging.2011.06.022 (2012).
36. Watts, J. C. et al. Transmission of multiple system atrophy prions to transgenic mice. Proc Natl Acad Sci USA 110, 19555-19560, doi: 10.1073/pnas.1318268110 (2013).
37. Guillot-Sestier, M. V., Sunyach, C., Druon, C., Scarzello, S. & Checler, F. The alpha-secretase-derived N-terminal product of cellular prion, N1, displays neuroprotective function in vitro and in vivo. J Biol Chem 284, 35973-35986, doi: 10.1074/jbc.M109.051086 (2009).
38. Altmeppen, H. C. et al. Proteolytic processing of the prion protein in health and disease. Am J Neurodegener Dis 1, 15-31 (2012).
39. Ezrin-Waters, C., Resch, L. & Lang, A. E. Coexistence of idiopathic Parkinson's disease and Creutzfeldt-Jakob disease. Can J Neurol Sci 12, 272-273 (1985).
40. Iida, T., Doh-ura, K., Kawashima, T., Abe, H. & Iwaki, T. An atypical case of sporadic Creutzfeldt-Jakob disease with Parkinson's disease. Neuropathology 21, 294-297 (2001).
41. Haik, S. et al. Alpha-synuclein-immunoreactive deposits in human and animal prion diseases. Acta Neuropathol 103, 516-520, doi: 10.1007/s00401-001-0499-z (2002).
42. Vital, A., Canron, M. H., Gil, R., Hauw, J. J. & Vital, C. A sporadic case of Creutzfeldt-Jakob disease with beta-amyloid deposits and alpha-synuclein inclusions. Neuropathology 27, 273-277 (2007).
43. Haraguchi, T. et al. Coexistence of Creutzfeldt-Jakob disease, Lewy body disease, and Alzheimer's disease pathology: an autopsy case showing typical clinical features of Creutzfeldt-Jakob disease. Neuropathology 29, 454-459, doi: 10.1111/j.1440-1789.2008.00964.x (2009).
44. Peretz, D. et al. Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412, 739-743, doi: 10.1038/35089090 (2001).