Monomeric α-synuclein (αS) inhibits amyloidogenesis of human prion protein (hPrP) by forming a stable αS-hPrP hetero-dimer.

References

• Chiti F, Dobson CM. Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem. 2006;75(1):333–366.
   PubMedGoogle Scholar
• Legname G, Baskakov IV, Nguyen HO, et al. Synthetic mammalian prions. Science. 2004;305(5684):673–676. .
   PubMed Web of Science ®Google Scholar
• Riek R, Guntert P, Dobeli H, et al. NMR studies in aqueous solution fail to identify significant conformational differences between the monomeric forms of two Alzheimer peptides with widely different plaque-competence, A beta(1-40)(ox) and A beta(1-42)(ox). Eur J Biochem. 2001;268:5930–5936.
   PubMedGoogle Scholar
• Shtilerman MD, Ding TT, Lansbury PT, Jr. Molecular crowding accelerates fibrillization of alpha-synuclein: could an increase in the cytoplasmic protein concentration induce Parkinson’s disease? Biochemistry-Us. 2002;41:3855–3860.
   PubMed Web of Science ®Google Scholar
• Prusiner SB. Molecular biology of prion diseases. Science. 1991;252:1515–1522.
   PubMed Web of Science ®Google Scholar
• Morales R, Moreno-Gonzalez I, Soto C. Cross-seeding of misfolded proteins: implications for etiology and pathogenesis of protein misfolding diseases. PLoS Pathog. 2013;9:e1003537.
   PubMed Web of Science ®Google Scholar
• O’Nuallain B, Williams AD, Westermark P, et al. Seeding specificity in amyloid growth induced by heterologous fibrils. J Biol Chem. 2004;279:17490–17499.
   PubMed Web of Science ®Google Scholar
• Lauren J, Gimbel DA, Nygaard HB, et al. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009;457:1128–U84.
   PubMed Web of Science ®Google Scholar
• Kessels HW, Nguyen LN, Nabavi S, et al. The prion protein as a receptor for amyloid-beta. Nature. 2010;466: E3–4. discussion E-5.
   PubMed Web of Science ®Google Scholar
• Kim TD, Paik SR, Yang CH, et al. Structural changes in alpha-synuclein affect its chaperone-like activity in vitro. Protein Sci. 2000;9(12):2489–2496.
   PubMed Web of Science ®Google Scholar
• Souza JM, Giasson BI, Lee VM, et al. Chaperone-like activity of synucleins. FEBS Lett. 2000;474(1):116–119.
   PubMed Web of Science ®Google Scholar
• Ahn M, Kim S, Kang M, et al. Chaperone-like activities of alpha-synuclein: alpha-synuclein assists enzyme activities of esterases. Biochem Biophys Res Commun. 2006;346(4):1142–1149.
   PubMed Web of Science ®Google Scholar
• Manda KM, Yedlapudi D, Korukonda S, et al. The chaperone-like activity of alpha-synuclein attenuates aggregation of its alternatively spliced isoform, 112-synuclein in vitro: plausible cross-talk between isoforms in protein aggregation. PLoS One. 2014;9(6):e98657.
   PubMed Web of Science ®Google Scholar
• Shirasaka M, Kuwata K, Honda R. alpha-Synuclein chaperone suppresses nucleation and amyloidogenesis of prion protein. Biochem Biophys Res Commun. 2020;521(1):259–264.
   PubMed Web of Science ®Google Scholar
• Aulic S, Masperone L, Narkiewicz J, et al. alpha-synuclein amyloids hijack prion protein to gain cell entry, facilitate cell-to-cell spreading and block prion replication. Sci Rep. 2017;7(1):10050. .
   PubMed Web of Science ®Google Scholar
• Ando T, Uchihashi T, Kodera N, et al. High-speed AFM and nano-visualization of biomolecular processes. Pflugers Arch. 2008;456(1):211–225. .
   PubMed Web of Science ®Google Scholar
• Kakuda K, Niwa A, Honda R, et al. A DISC1 point mutation promotes oligomerization and impairs information processing in a mouse model of schizophrenia. J Biochem. 2019;165(4):369–378. .
   PubMed Web of Science ®Google Scholar
• Kakuda K, Yamaguchi K-I, Kuwata K, et al. A valine-to-lysine substitution at position 210 induces structural conversion of prion protein into a β-sheet rich oligomer. Biochem Biophys Res Commun. 2018;506(1):81–86.
   PubMed Web of Science ®Google Scholar
• Streets AM, Sourigues Y, Kopito RR, et al. Simultaneous measurement of amyloid fibril formation by dynamic light scattering and fluorescence reveals complex aggregation kinetics. PLoS One. 2013;8(1):e54541.
   PubMed Web of Science ®Google Scholar
• Cho KR, Huang Y, Yu S, et al. A multistage pathway for human prion protein aggregation in vitro: from multimeric seeds to beta-oligomers and nonfibrillar structures. J Am Chem Soc. 2011;133(22):8586–8593. .
   PubMed Web of Science ®Google Scholar
• Nelson R, Sawaya MR, Balbirnie M, et al. Structure of the cross-beta spine of amyloid-like fibrils. Nature. 2005;435(7043):773–778. .
   PubMed Web of Science ®Google Scholar
• Knowles TP, Waudby CA, Devlin GL, et al. An analytical solution to the kinetics of breakable filament assembly. Science. 2009;326(5959):1533–1537. .
   PubMed Web of Science ®Google Scholar
• Zhang Y, Hashemi M, Lv Z, et al. High-speed atomic force microscopy reveals structural dynamics of alpha-synuclein monomers and dimers. J Chem Phys. 2018;148(12):123322. .
   PubMed Web of Science ®Google Scholar
• Fauvet B, Mbefo MK, Fares MB, et al. alpha-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J Biol Chem. 2012;287(19):15345–15364. .
   PubMed Web of Science ®Google Scholar
• Bhattacharya S, Xu L, Thompson D. Long-range regulation of partially folded amyloidogenic peptides. Sci Rep. 2020;10:7597.
   PubMed Web of Science ®Google Scholar
• Wu KP, Baum J. Backbone assignment and dynamics of human alpha-synuclein in viscous 2 M glucose solution. Biomol NMR Assign. 2011;5:43–46.
   PubMed Web of Science ®Google Scholar
• Kamatari YO, Hayano Y, Yamaguchi K, et al. Characterizing antiprion compounds based on their binding properties to prion proteins: implications as medical chaperones. Protein Sci. 2013;22:22–34.
   PubMed Web of Science ®Google Scholar
• Chandra S, Gallardo G, Fernandez-Chacon R, et al. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell. 2005;123:383–396.
   PubMed Web of Science ®Google Scholar
• Rekas A, Adda CG, Andrew Aquilina J, et al. Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein: effects on amyloid fibril formation and chaperone activity. J Mol Biol. 2004;340:1167–1183.
   PubMed Web of Science ®Google Scholar
• Park SM, Jung HY, Kim TD, et al. Distinct roles of the N-terminal-binding domain and the C-terminal-solubilizing domain of alpha-synuclein, a molecular chaperone. J Biol Chem. 2002;277:28512–28520.
   PubMed Web of Science ®Google Scholar
• Janowska MK, Wu KP, Baum J. Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein. Sci Rep. 2015;5:15164.
   PubMed Web of Science ®Google Scholar
• Arosio P, Michaels TC, Linse S, et al. Kinetic analysis reveals the diversity of microscopic mechanisms through which molecular chaperones suppress amyloid formation. Nat Commun. 2016;7:10948.
   PubMed Web of Science ®Google Scholar
• Bistaffa E, Rossi M, Cmg DL, et al. Prion efficiently replicates in alpha-synuclein knockout mice. Mol Neurobiol. 2019;56:7448–7457.
   PubMed Web of Science ®Google Scholar
• Hashimoto M, Ho G, Takamatsu Y, et al. Understanding Creutzfeldt-Jackob disease from a viewpoint of amyloidogenic evolvability. Prion. 2020;14:1–8.
   PubMed Web of Science ®Google Scholar
• Yamaguchi K, Kamatari YO, Ono F, et al. A designer molecular chaperone against transmissible spongiform encephalopathy slows disease progression in mice and macaques. Nat Biomed Eng. 2019;3:206–219.
   PubMed Web of Science ®Google Scholar