Abstract
α-Synuclein fibrillation is now regarded as a major pathogenic process in Parkinson’s disease and its proteinaceous deposits are also detected in other neurological disorders including Alzheimer's disease. Therefore anti-amyloidegenic compounds may delay or prevent the progression of synucleinopathies disease. Molecular chaperones are group of proteins which mediate correct folding of proteins by preventing unsuitable interactions which may lead to aggregation. The objective of this study was to investigate the anti-amyloidogenic effect of molecular chaperone artemin on α-synuclein. As the concentration of artemin was increased up to 4 μg/ml, a decrease in fibril formation of α-synuclein was observed using thioflavin T (ThT) fluorescence and congo red (CR) assay. Transmission electron microscopy (TEM) images also demonstrated a reduction in fibrils in the presence of artemin. The secondary structure of α-synuclein was similar to its native form prior to fibrillation when incubated with artemin. A cell-based assay has shown that artemin inhibits α-synuclein aggregation and reduce cytotoxicity, apoptosis and reactive oxygen species (ROS) production. Our results revealed that artemin has efficient chaperon activity for preventing α-synuclein fibril formation and toxicity.
Funding source: Tarbiat Modares University
Funding source: Iranian National Science Foundation
Award Identifier / Grant number: 93042561
Acknowledgments
We gratefully appreciate the research council of Tarbiat Modares University and Iranian National Science Foundation (INSF, project 93042561) for their financial support through this investigation.
Conflict of interest statement: The authors declare no competing interest.
References
Ahsan, N., Mishra, S., Jain, M.K., Surolia, A., and Gupta, S. (2015). Curcumin pyrazole and its derivative (N-(3-nitrophenylpyrazole) curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of wild type and mutant α-synuclein. Sci. Rep. 5: 9862, https://doi.org/10.1038/srep09862.Search in Google Scholar PubMed PubMed Central
Anguiano, M., Nowak, R.J., and Lansbury, P.T. (2002). Protofibrillar islet amyloid polypeptide permeabilizes synthetic vesicles by a pore-like mechanism that may be relevant to type II diabetes. Biochemistry 41: 11338–11343, https://doi.org/10.1021/bi020314u.Search in Google Scholar PubMed
Arispe, N. (2004). Architecture of the Alzheimer's AβP ion channel pore. J. Membr. Biol. 197: 33–48, https://doi.org/10.1007/s00232-003-0638-7.Search in Google Scholar PubMed
Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248–254, https://doi.org/10.1006/abio.1976.9999.Search in Google Scholar PubMed
Breydo, L., Wu, J.W., and Uversky, V.N. (2012). α-Synuclein misfolding and Parkinson's disease. Biochim. Biophys. Acta. 1822: 261–285, https://doi.org/10.1016/j.bbadis.2011.10.002.Search in Google Scholar PubMed
Chen, T., Villeneuve, T.S., Garant, K.A., Amons, R., and MacRae, T.H. (2007). Functional characterization of artemin, a ferritin homolog synthesized in Artemia embryos during encystment and diapause. FEBS J. 274: 1093–1101, https://doi.org/10.1111/j.1742-4658.2007.05659.x.Search in Google Scholar PubMed
Congdon, E.E., Necula, M., Blackstone, R.D., and Kuret, J. (2007). Potency of a tau fibrillization inhibitor is influenced by its aggregation state. Arch. Biochem. Biophys. 465: 127–135, https://doi.org/10.1016/j.abb.2007.05.004.Search in Google Scholar PubMed PubMed Central
Conte, A., Pellegrini, S., and Tagliazucchi, D. (2003). Synergistic protection of PC12 cells from β-amyloid toxicity by resveratrol and catechin. Brain Res. Bull. 62: 29–38, https://doi.org/10.1016/j.brainresbull.2003.08.001.Search in Google Scholar PubMed
Cox, D., Carver, J.A., and Ecroyd, H. (2014). Preventing α-synuclein aggregation: the role of the small heat-shock molecular chaperone proteins. Biochim. Biophys. Acta. 1842: 1830–1843, https://doi.org/10.1016/j.bbadis.2014.06.024.Search in Google Scholar PubMed
Dehay, B., Bourdenx, M., Gorry, P., Przedborski, S., Vila, M., Hunot, S., Singleton, A., Olanow, C.W., Merchant, K.M., Bezard, E., et al. (2015). Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations. Lancet Neurol 14: 855–866, https://doi.org/10.1016/S1474-4422(15)00006-X.Search in Google Scholar PubMed PubMed Central
Fink, A.L. (1998). Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold. Des. 3: R9–R23, http://doi.org/10.1016/S1359-0278(98)00002-9.10.1016/S1359-0278(98)00002-9Search in Google Scholar PubMed
Fink, A.L. (2006). The aggregation and fibrillation of α-synuclein. Acc. Chem. Res. 39: 628–634l, https://doi.org/10.1021/ar050073t.Search in Google Scholar PubMed
Friesen, E.L., De Snoo, M.L., Rajendran, L., Kalia, L.V., and Kalia, S.K. (2017). Chaperone-based therapies for disease modification in Parkinson's disease. Park. Dis. 2017: 5015307, https://doi.org/10.1155/2017/5015307.Search in Google Scholar PubMed PubMed Central
Giehm, L., Lorenzen, N., and Otzen, D.E. (2011). Assays for α-synuclein aggregation. Methods 53: 295–305, https://doi.org/10.1016/j.ymeth.2010.12.008.Search in Google Scholar PubMed
Hansen, C., Angot, E., Bergström, A.L., Steiner, J.A., Pieri, L., Paul, G., Outeiro, T.F., Melki, R., Kallunki, P., and Fog, K. (2011). α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J. Clin. Invest 121: 715–725, https://doi.org/10.1172/JCI43366.Search in Google Scholar PubMed PubMed Central
Hassani, L., and Sajedi, R.H. (2013). Effect of artemin on structural transition of β-lactoglobulin. Spectrochim Acta Part A Mol. Biomol. Spectrosc 105: 24–28, https://doi.org/10.1016/j.saa.2012.12.003.Search in Google Scholar PubMed
Honarmand, S., Dabirmanesh, B., Amanlou, M., and Khajeh, K. (2019). The interaction of several herbal extracts with α-synuclein: Fibril formation and surface plasmon resonance analysis. PLoS One 14: e0217801, https://doi.org/10.1371/journal.pone.0217801.Search in Google Scholar PubMed PubMed Central
Jellinger, K.A. (2001). Cell death mechanisms in neurodegeneration. J. Cell. Mol. Med. 5: 1–17, https://doi.org/10.1111/j.1582-4934.2001.tb00134.x.Search in Google Scholar PubMed PubMed Central
Jellinger, K.A. (2010). Basic mechanisms of neurodegeneration: a critical update. J. Cell. Mol. Med. 14: 457–487, https://doi.org/10.1111/j.1582-4934.2010.01010.x.Search in Google Scholar PubMed PubMed Central
Khosravi, Z., Khalili, M.A.N., Moradi, S., Hassan Sajedi, R., and Zeinoddini, M. (2018). The molecular chaperone artemin efficiently blocks fibrillization of TAU protein in vitro. Cell. J. 19: 569, https://doi.org/10.22074/cellj.2018.4510.Search in Google Scholar PubMed PubMed Central
Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227: 680, https://doi.org/10.1038/227680a0.Search in Google Scholar PubMed
Maiti, P., Manna, J., Veleri, S., and Frautschy, S. (2014). Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin. Biomed. Res. Int. 2014: 14, https://doi.org/10.1155/2014/495091.Search in Google Scholar PubMed PubMed Central
Melki, R. (2018). Alpha-synuclein and the prion hypothesis in Parkinson's disease. Rev. Neurol 174: 644–652, https://doi.org/10.1016/j.neurol.2018.08.002.Search in Google Scholar PubMed
Narkiewicz, J., Giachin, G., and Legname, G. (2014). In vitro aggregation assays for the characterization of α-synuclein prion-like properties. Prion 8: 19–32, https://doi.org/10.4161/pri.28125.Search in Google Scholar PubMed PubMed Central
Porat, Y., Abramowitz, A., and Gazit, E. (2006). Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem. Biol. Drug. Des. 67: 27–37, https://doi.org/10.1111/j.1747-0285.2005.00318.x.Search in Google Scholar PubMed
Sashourpour, M., Zahri, S., Radjabian, T., Ruf, V., Pan-Montojo, F., and Morshedi, D. (2017). A study on the modulation of alpha-synuclein fibrillation by Scutellaria pinnatifida extracts and its neuroprotective properties. PLoS One. 12: e0184483, https://doi.org/10.1371/journal.pone.0184483.Search in Google Scholar PubMed PubMed Central
Selkoe, D.J. (2004). Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nat. Cell. Biol. 6: 1054–1061, https://doi.org/10.1038/ncb1104-1054.Search in Google Scholar PubMed
Shahangian, S.S., Rasti, B., Hasan Sajedi, R., Khodarahmi, R., Taghdir, M., and Ranjbar, B. (2011). Artemin as an efficient molecular chaperone. Protein J. 30: 549–557, https://doi.org/10.1007/s10930-011-9359-4.Search in Google Scholar PubMed
Stefani, M. (2012). Structural features and cytotoxicity of amyloid oligomers: implications in Alzheimer's disease and other diseases with amyloid deposits. Prog. Neurobiol 99: 226–245, https://doi.org/10.1016/j.pneurobio.2012.03.002.Search in Google Scholar PubMed
Surmeier, D.J., Obeso, J.A., and Halliday, G.M. (2017). Parkinson's disease is not simply a prion disorder. J. Neurosci. 37: 9799–807, https://doi.org/10.1523/JNEUROSCI.1787-16.2017.Search in Google Scholar PubMed PubMed Central
Sweeney, P., Park, H., Baumann, M., Dunlop, J., Frydman, J., Kopito, R., McCampbell, A., Leblanc, G., Venkateswaran, A., and Nurmi, A. (2017). Protein misfolding in neurodegenerative diseases: implications and strategies. Transl. Neurodegener 6: 6, https://doi.org/10.1186/s40035-017-0077-5.Search in Google Scholar PubMed PubMed Central
Uversky, V.N. (2002) What does it mean to be natively unfolded? Eur. J. Biochem. 269: 2–12, https://doi.org/10.1046/j.0014-2956.2001.02649.x.Search in Google Scholar PubMed
Uversky, V.N. and Fink, A.L. (2004). Conformational constraints for amyloid fibrillation: the importance of being unfolded. Biochim. Biophys. Acta. 1698: 131–153, https://doi.org/10.1016/j.bbapap.2003.12.008.Search in Google Scholar PubMed
Uversky, V.N., Li, J., and Fink, A.L. (2001a). Pesticides directly accelerate the rate of α-synuclein fibril formation: a possible factor in Parkinson's disease. FEBS Lett. 500: 105–108, https://doi.org/10.1016/s0014-5793(01)02597-2.Search in Google Scholar PubMed
Uversky, V.N., Li, J., and Fink, A.L. (2001b). Evidence for a partially folded intermediate in α-synuclein fibril formation. J. Biol. Chem. 276: 10737–10744, https://doi.org/10.1074/jbc.M010907200.Search in Google Scholar PubMed
Vashist, S., Cushman, M., and Shorter, J. (2010). Applying Hsp104 to protein-misfolding disorders. Biochem. Cell. Biol. 88: 1–13.10.1139/O09-121Search in Google Scholar PubMed PubMed Central
Warner, A.H., Brunet, R.T., MacRae, T.H., and Clegg, J.S. (2004). Artemin is an RNA-binding protein with high thermal stability and potential RNA chaperone activity. Arch. Biochem. Biophys. 424: 189–200, https://doi.org/10.1016/j.abb.2004.02.022.Search in Google Scholar PubMed
Xu, L. and Pu, J. (2016). Alpha-synuclein in Parkinson's disease: from pathogenetic dysfunction to potential clinical application. Park. Dis. 2016: 10, https://doi.org/10.1155/2016/1720621.Search in Google Scholar PubMed PubMed Central
Zhang, H., Xu, L.-Q., and Perrett, S. (2011). Studying the effects of chaperones on amyloid fibril formation. Methods 53: 285–294, https://doi.org/10.1016/j.ymeth.2010.11.009.Search in Google Scholar PubMed
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Reviews
- Small dense low-density lipoprotein-lowering agents
- The piRNA pathway in planarian flatworms: new model, new insights
- Research Articles
- Anti-amyloidogenic effect of artemin on α-synuclein
- Galectin-3 is modulated in pancreatic cancer cells under hypoxia and nutrient deprivation
- Role of protein tyrosine phosphatase 1B (PTP1B) in the increased sensitivity of endothelial cells to a promigratory effect of erythropoietin in an inflammatory environment
- Effects of extracellular Hsp70, lipopolysaccharide and lipoteichoic acid on human monocyte-derived macrophages and differentiated THP-1 cells
- High-mobility group box 3 (HMGB3) silencing inhibits non-small cell lung cancer development through regulating Wnt/β-catenin pathway
Articles in the same Issue
- Frontmatter
- Reviews
- Small dense low-density lipoprotein-lowering agents
- The piRNA pathway in planarian flatworms: new model, new insights
- Research Articles
- Anti-amyloidogenic effect of artemin on α-synuclein
- Galectin-3 is modulated in pancreatic cancer cells under hypoxia and nutrient deprivation
- Role of protein tyrosine phosphatase 1B (PTP1B) in the increased sensitivity of endothelial cells to a promigratory effect of erythropoietin in an inflammatory environment
- Effects of extracellular Hsp70, lipopolysaccharide and lipoteichoic acid on human monocyte-derived macrophages and differentiated THP-1 cells
- High-mobility group box 3 (HMGB3) silencing inhibits non-small cell lung cancer development through regulating Wnt/β-catenin pathway