Phospholipids as inhibitors of amyloid fibril formation
Keywords:
amyloid fibrils of lysozyme/insulin, inhibition, nucleation, oxidized phospholipids, Thioflavin T
Abstract
Amyloid fibrils are the protein aggregates, whose formation is involved in the pathogenesis of Alzheimer’s disease, systemic amyloidosis, etc. Since there is no effective ways to treat these diseases, developing the new anti-amyloid drugs is of great importance. In this study a series of phospholipids have been tested for their ability to inhibit lysozyme and insulin amyloid fibril formation at acidic or neutral pH and elevated temperature. The lag time, elongation rate and fibrillization extent were estimated using Thioflavin T fluorescence assay. It is found that the oxidized and charged phospholipids, included into the liposomes, were the most effective inhibitors of the protein fibrillization. By comparing the magnitude and direction of the lipid effect in different lipid-protein systems it was concluded that the reduction of the amyloid fibril formation is governed by hydrophobic and specific liposome-protein interactions. It is hypothesized that the presence of the surface formed by the lipid polar heads is critical for reducing the protein fibrillization extent.Downloads
Download data is not yet available.
References
1. Caughey B. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders / B. Caughey, P.T. Lansbury // Annu. Rev. Neurosci. – 2003. – V. 26. – P. 267–298.
2. Selkoe D. J. Folding proteins in fatal ways / D.J. Selkoe // Nature. – 2003. – V. 426. – P. 900–904.
3. Mason J.M. Design strategies for anti-amyloid agents / J.M. Mason, N. Kokkoni, K. Stott, A.J. Doig // Curr. Opin. Struct. Biol. – 2003. – V. 13. – P. 526–532.
4. Macht D.I. Experimental studies on heparin and its influence on toxicity of digitaloids, congo red, cobra venom and other drugs / D.I. Macht // Ann. Intern. Med. – 1943. – Vol. 18. – P. 772–791.
5. Amini R. Apigenin reduces human insulin fibrillation in vitro and protectsSK-N-MC cells against insulin amyloids / R. Amini, R. Yazdanparast, S. Bahramikia // Int. J. Biol. Macromol. – 2013. – V. 60. – P. 334–40.
6. Small molecule inhibitors of α-synuclein filament assembly / M. Masuda, N. Suzuki, S. Taniguchi [et al.] // Biochemistry. – 2006. – V. 45. – P. 6085–6094.
7. Cardoso I. 4-iodo-4-Deoxydoxorubicin and tetracyclines disrupt transthyretin amyloid fibrils in vitro producing noncytotoxic species: screening for TTR fibril disrupters / I. Cardoso, G. Merlini, M.J. Saraiva // FASEB J. – 2003. – V. 17. – P. 803–809.
8. Studies of anti-fibrillogenic activity of phthalocyanines of zirconium containing out-of-plane ligands / V. Kovalska, M. Losytskyy, V. Chernii [et al.] // Bioorg. Med. Chem. – 2012. – V. 20. – P. 330–334.
9. Oligo(ethylene glycol) Derivatives of Thioflavin T as inhibitors of protein–amyloid interactions / P. Inbar, C.Q. Li, S.A. Takayama [et al.] // Chem. Bio. Chem. – 2006. – V. 7. – P. 1563–1566.
10. Kumar E.K. Differential effects of ionic and non-ionic surfactants on lysozyme fibrillation / E.K. Kumar, N.P. Prabhu // Phys. Chem. Chem. Phys. – 2014. – V. 16. – P. 24076–24088.
11. Wang S.S.-S. Amyloid fibrillation and cytotoxicity of insulin are inhibited by the amphiphilic surfactants / S.S.-S. Wang, K.-N. Liu, T.-C. Han // Biochim. Biophys. Acta. – 2010. – V. 1802. – P. 519–530.
12. Stefani M. Protein folding and misfolding on surfaces / M. Stefani // Int J Mol Sci. – 2008. – V. 9. – P. 2515–2542.
13. How is protein aggregation in amyloidogenic diseases modulated by biological membranes / C. Aisenbrey, T. Borowik, R. Byström [et al.] // Eur. Biophys. J. – 2008. – V. 37. – P. 247– 255.
14. Kinnunen P.K. Proteinoxidized phospholipid interactions in cellular signaling for cell death: from biophysics to clinical correlations / P.K. Kinnunen, K. Kaarniranta, A.K. Mahalka // Biochim. Biophys. Acta. – 2012. – V. 1818. – P. 2446–2455.
15. Uversky V.N. Conformational constraints for amyloid fibrillation: the importance of being unfolded / V.N. Uversky, A.L. Fink // Biochim. Biophys. Acta. – 2004. – V. 1698. – P. 131–153.
16. Fluorescence monitoring of the effect of oxidized lipids on the process of protein fibrillization / K. Vus, R. Sood, G. Gorbenko [et al.] // Method. Appl. Fluor. – 2016. – V. 4. –P. 034008.
17. Amyloid fibril formation and seeding by wild-type human lysozyme and its disease-related mutational variants / L.A. Morozova-Roche, J. Zurdo, A. Spencer [et al.] // J. Struct. Biol. – 2000. – V. 130. – P. 339–351.
2. Selkoe D. J. Folding proteins in fatal ways / D.J. Selkoe // Nature. – 2003. – V. 426. – P. 900–904.
3. Mason J.M. Design strategies for anti-amyloid agents / J.M. Mason, N. Kokkoni, K. Stott, A.J. Doig // Curr. Opin. Struct. Biol. – 2003. – V. 13. – P. 526–532.
4. Macht D.I. Experimental studies on heparin and its influence on toxicity of digitaloids, congo red, cobra venom and other drugs / D.I. Macht // Ann. Intern. Med. – 1943. – Vol. 18. – P. 772–791.
5. Amini R. Apigenin reduces human insulin fibrillation in vitro and protectsSK-N-MC cells against insulin amyloids / R. Amini, R. Yazdanparast, S. Bahramikia // Int. J. Biol. Macromol. – 2013. – V. 60. – P. 334–40.
6. Small molecule inhibitors of α-synuclein filament assembly / M. Masuda, N. Suzuki, S. Taniguchi [et al.] // Biochemistry. – 2006. – V. 45. – P. 6085–6094.
7. Cardoso I. 4-iodo-4-Deoxydoxorubicin and tetracyclines disrupt transthyretin amyloid fibrils in vitro producing noncytotoxic species: screening for TTR fibril disrupters / I. Cardoso, G. Merlini, M.J. Saraiva // FASEB J. – 2003. – V. 17. – P. 803–809.
8. Studies of anti-fibrillogenic activity of phthalocyanines of zirconium containing out-of-plane ligands / V. Kovalska, M. Losytskyy, V. Chernii [et al.] // Bioorg. Med. Chem. – 2012. – V. 20. – P. 330–334.
9. Oligo(ethylene glycol) Derivatives of Thioflavin T as inhibitors of protein–amyloid interactions / P. Inbar, C.Q. Li, S.A. Takayama [et al.] // Chem. Bio. Chem. – 2006. – V. 7. – P. 1563–1566.
10. Kumar E.K. Differential effects of ionic and non-ionic surfactants on lysozyme fibrillation / E.K. Kumar, N.P. Prabhu // Phys. Chem. Chem. Phys. – 2014. – V. 16. – P. 24076–24088.
11. Wang S.S.-S. Amyloid fibrillation and cytotoxicity of insulin are inhibited by the amphiphilic surfactants / S.S.-S. Wang, K.-N. Liu, T.-C. Han // Biochim. Biophys. Acta. – 2010. – V. 1802. – P. 519–530.
12. Stefani M. Protein folding and misfolding on surfaces / M. Stefani // Int J Mol Sci. – 2008. – V. 9. – P. 2515–2542.
13. How is protein aggregation in amyloidogenic diseases modulated by biological membranes / C. Aisenbrey, T. Borowik, R. Byström [et al.] // Eur. Biophys. J. – 2008. – V. 37. – P. 247– 255.
14. Kinnunen P.K. Proteinoxidized phospholipid interactions in cellular signaling for cell death: from biophysics to clinical correlations / P.K. Kinnunen, K. Kaarniranta, A.K. Mahalka // Biochim. Biophys. Acta. – 2012. – V. 1818. – P. 2446–2455.
15. Uversky V.N. Conformational constraints for amyloid fibrillation: the importance of being unfolded / V.N. Uversky, A.L. Fink // Biochim. Biophys. Acta. – 2004. – V. 1698. – P. 131–153.
16. Fluorescence monitoring of the effect of oxidized lipids on the process of protein fibrillization / K. Vus, R. Sood, G. Gorbenko [et al.] // Method. Appl. Fluor. – 2016. – V. 4. –P. 034008.
17. Amyloid fibril formation and seeding by wild-type human lysozyme and its disease-related mutational variants / L.A. Morozova-Roche, J. Zurdo, A. Spencer [et al.] // J. Struct. Biol. – 2000. – V. 130. – P. 339–351.
Cited
How to Cite
Vus, K. O., Trusova, V. M., Gorbenko, G. P., & Kinnunen, P. (1). Phospholipids as inhibitors of amyloid fibril formation. Biophysical Bulletin, 2(36), 37-42. https://doi.org/10.26565/2075-3810-2016-36-05
Section
Molecular biophysics
Copyright (c) 2016 Vus K.O., Trusova V.M., Gorbenko G.P., Kinnunen P.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
