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Recent developments in cell-based assays and stem cell technologies for botulinum neurotoxin research and drug discovery

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References

  • Tighe AP, Schiavo G. Botulinum neurotoxins: mechanism of action. Toxicon 67, 87–93 (2013).
  • Montal M. Botulinum neurotoxin: a marvel of protein design. Annu. Rev. Biochem. 79, 591–617 (2010).
  • Dover N, Barash JR, Hill KK, Xie G, Arnon SS. Molecular characterization of a novel botulinum neurotoxin type H gene. J. Infect. Dis. doi:10.1093/infdis/jit450 (2013) ( Epub ahead of print).
  • Arnon SS, Schechter R, Inglesby TV et al. Botulinum toxin as a biological weapon: medical and public health management. JAMA 285(8), 1059–1070 (2001).
  • Wein LM, Liu Y. Analyzing a bioterror attack on the food supply: the case of botulinum toxin in milk. Proc. Natl Acad. Sci. USA 102(28), 9984–9989 (2005).
  • Hakami RM, Ruthel G, Stahl AM, Bavari S. Gaining ground: assays for therapeutics against botulinum neurotoxin. Trends Microbiol. 18(4), 164–172 (2010).
  • Burnett JC, Henchal EA, Schmaljohn AL, Bavari S. The evolving field of biodefence: therapeutic developments and diagnostics. Nat. Rev. Drug Discov. 4(4), 281–297 (2005).
  • Chen S. Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins 4(10), 913–939 (2012).
  • Pellett S. Learning from the past: historical aspects of bacterial toxins as pharmaceuticals. Curr. Opin. Microbiol. 15(3), 292–299 (2012).
  • Carruthers A, Carruthers J. Botulinum toxin products overview. Skin Therapy Lett. 13(6), 1–4 (2008).
  • Schenone M, Dancik V, Wagner BK, Clemons PA. Target identification and mechanism of action in chemical biology and drug discovery. Nat. Chem. Biol. 9(4), 232–240 (2013).
  • Schmidt JJ, Stafford RG, Millard CB. High-throughput assays for botulinum neurotoxin proteolytic activity: serotypes A, B, D, and F. Anal. Biochem. 296(1), 130–137 (2001).
  • Burnett JC, Schmidt JJ, Stafford RG et al. Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity. Biochem. Biophys. Res. Commun. 310(1), 84–93 (2003).
  • Pellett S. Progress in cell based assays for botulinum neurotoxin detection. Curr. Top. Microbiol. Immunol. 364, 257–285 (2013).
  • Lee JA, Chu S, Willard FS et al. Open innovation for phenotypic drug discovery: The PD2 assay panel. J. Biomol. Screen. 16(6), 588–602 (2011).
  • Swinney DC, Anthony J. How were new medicines discovered? Nat. Rev. Drug Discov. 10(7), 507–519 (2011).
  • Kalandakanond S, Coffield JA. Cleavage of SNAP-25 by botulinum toxin type A requires receptor-mediated endocytosis, pH-dependent translocation, and zinc. J. Pharmacol. Exp. Ther. 296(3), 980–986 (2001).
  • Apland JP, Adler M, Oyler GA. Inhibition of neurotransmitter release by peptides that mimic the N-terminal domain of SNAP-25. J. Protein Chem. 22(2), 147–153 (2003).
  • Blasi J, Chapman ER, Link E et al. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 365(6442), 160–163 (1993).
  • Apland JP, Biser JA, Adler M et al. Peptides that mimic the carboxy-terminal domain of SNAP-25 block acetylcholine release at an Aplysia synapse. J. Appl. Toxicol. 19(Suppl. 1), S23–S26 (1999).
  • Bajohrs M, Rickman C, Binz T, Davletov B. A molecular basis underlying differences in the toxicity of botulinum serotypes A and E. EMBO Rep. 5(11), 1090–1095 (2004).
  • Pellett S, Tepp WH, Toth SI, Johnson EA. Comparison of the primary rat spinal cord cell (RSC) assay and the mouse bioassay for botulinum neurotoxin type A potency determination. J. Pharmacol. Toxicol. Methods 61(3), 304–310 (2010).
  • Nuss JE, Ruthel G, Tressler LE et al. Development of cell-based assays to measure botulinum neurotoxin serotype A activity using cleavage-sensitive antibodies. J. Biomol. Screen. 15(1), 42–51 (2010).
  • Sheridan RE, Smith TJ, Adler M. Primary cell culture for evaluation of botulinum neurotoxin antagonists. Toxicon 45(3), 377–382 (2005).
  • Coffield JA, Yan X. Neuritogenic actions of botulinum neurotoxin A on cultured motor neurons. J. Pharmacol. Exp. Ther. 330(1), 352–358 (2009).
  • Stahl AM, Ruthel G, Torres-Melendez E et al. Primary cultures of embryonic chicken neurons for sensitive cell-based assay of botulinum neurotoxin: implications for therapeutic discovery. J. Biomol. Screen. 12(3), 370–377 (2007).
  • Dong M, Tepp WH, Johnson EA, Chapman ER. Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in living cells. Proc. Natl Acad. Sci. USA 101(41), 14701–14706 (2004).
  • Pellett S, Tepp WH, Clancy CM, Borodic GE, Johnson EA. A neuronal cell-based botulinum neurotoxin assay for highly sensitive and specific detection of neutralizing serum antibodies. FEBS Lett. 581(25), 4803–4808 (2007).
  • Pellett S, Du ZW, Pier CL et al. Sensitive and quantitative detection of botulinum neurotoxin in neurons derived from mouse embryonic stem cells. Biochem. Biophys. Res. Commun. 404(1), 388–392 (2010).
  • Whitemarsh RC, Strathman MJ, Chase LG et al. Novel application of human neurons derived from induced pluripotent stem cells for highly sensitive botulinum neurotoxin detection. Toxicol. Sci. 126(2), 426–435 (2012).
  • McNutt P, Celver J, Hamilton T, Mesngon M. Embryonic stem cell-derived neurons are a novel, highly sensitive tissue culture platform for botulinum research. Biochem. Biophys. Res. Commun. 405(1), 85–90 (2011).
  • Kiris E, Nuss JE, Burnett JC et al. Embryonic stem cell-derived motoneurons provide a highly sensitive cell culture model for botulinum neurotoxin studies, with implications for high-throughput drug discovery. Stem Cell Res. 6(3), 195–205 (2011).
  • Grumelli C, Verderio C, Pozzi D et al. Internalization and mechanism of action of clostridial toxins in neurons. Neurotoxicology 26(5), 761–767 (2005).
  • Basavanna U, Muruvanda T, Brown EW, Sharma SK. Development of a cell-based functional assay for the detection of clostridium botulinum neurotoxin types A and E. Int. J. Microbiol. 2013, 593219 (2013).
  • Eubanks LM, Hixon MS, Jin W et al. An in vitro and in vivo disconnect uncovered through high-throughput identification of botulinum neurotoxin A antagonists. Proc. Natl Acad. Sci. USA 104(8), 2602–2607 (2007).
  • Yowler BC, Kensinger RD, Schengrund CL. Botulinum neurotoxin A activity is dependent upon the presence of specific gangliosides in neuroblastoma cells expressing synaptotagmin I. J. Biol. Chem. 277(36), 32815–32819 (2002).
  • Tsukamoto K, Arimitsu H, Ochi S et al. P19 embryonal carcinoma cells exhibit high sensitivity to botulinum type C and D/C mosaic neurotoxins. Microbiol. Immunol. 56(10), 664–672 (2012).
  • Purkiss JR, Friis LM, Doward S, Quinn CP. Clostridium botulinum neurotoxins act with a wide range of potencies on SH-SY5Y human neuroblastoma cells. Neurotoxicology 22(4), 447–453 (2001).
  • Hale M, Oyler G, Swaminathan S, Ahmed SA. Basic tetrapeptides as potent intracellular inhibitors of type A botulinum neurotoxin protease activity. J. Biol. Chem. 286(3), 1802–1811 (2011).
  • Fernandez-Salas E, Wang J, Molina Y et al. Botulinum neurotoxin serotype a specific cell-based potency assay to replace the mouse bioassay. PLoS ONE 7(11), e49516 (2012).
  • Tegenge MA, Bohnel H, Gessler F, Bicker G. Neurotransmitter vesicle release from human model neurons (NT2) is sensitive to botulinum toxin A. Cell. Mol. Neurobiol. 32(6), 1021–1029 (2012).
  • Whitemarsh RC, Pier CL, Tepp WH, Pellett S, Johnson EA. Model for studying Clostridium botulinum neurotoxin using differentiated motor neuron-like NG108-15 cells. Biochem. Biophys. Res. Commun. 427(2), 426–430 (2012).
  • Hong WS, Young EW, Tepp WH, Johnson EA, Beebe DJ. A microscale neuron and schwann cell coculture model for increasing detection sensitivity of botulinum neurotoxin type a. Toxicol. Sci. 134(1), 64–72 (2013).
  • Restani L, Giribaldi F, Manich M et al. Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons. PLoS Pathog. 8(12), e1003087 (2012).
  • Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon 38(2), 245–258 (2000).
  • Sun S, Suresh S, Liu H et al. Receptor binding enables botulinum neurotoxin B to sense low pH for translocation channel assembly. Cell Host Microbe 10(3), 237–247 (2011).
  • Dong M, Yeh F, Tepp WH et al. SV2 is the protein receptor for botulinum neurotoxin A. Science 312(5773), 592–596 (2006).
  • Verderio C, Grumelli C, Raiteri L et al. Traffic of botulinum toxins A and E in excitatory and inhibitory neurons. Traffic 8(2), 142–153 (2007).
  • Holtje M, Schulze S, Strotmeier J et al. Exchanging the minimal cell binding fragments of tetanus neurotoxin in botulinum neurotoxin A and B impacts their toxicity at the neuromuscular junction and central neurons. Toxicon 75, 108–121 (2013).
  • Kroken AR, Karalewitz AP, Fu Z, Kim JJ, Barbieri JT. Novel ganglioside-mediated entry of botulinum neurotoxin serotype D into neurons. J. Biol. Chem. 286(30), 26828–26837 (2011).
  • Keller JE, Cai F, Neale EA. Uptake of botulinum neurotoxin into cultured neurons. Biochemistry 43(2), 526–532 (2004).
  • Wiese S, Herrmann T, Drepper C et al. Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal cord of individual mouse embryos. Nat. Protoc. 5(1), 31–38 (2009).
  • Camu W, Henderson CE. Purification of embryonic rat motoneurons by panning on a monoclonal antibody to the low-affinity NGF receptor. J. Neurosci. Methods 44(1), 59–70 (1992).
  • Miles GB, Yohn DC, Wichterle H et al. Functional properties of motoneurons derived from mouse embryonic stem cells. J. Neurosci. 24(36), 7848–7858 (2004).
  • Wichterle H, Lieberam I, Porter JA, Jessell TM. Directed differentiation of embryonic stem cells into motor neurons. Cell 110(3), 385–397 (2002).
  • Wichterle H, Peljto M, Nedelec S. Xenotransplantation of embryonic stem cell-derived motor neurons into the developing chick spinal cord. Methods Mol. Biol. 482, 171–183 (2009).
  • Wichterle H, Peljto M. Differentiation of mouse embryonic stem cells to spinal motor neurons. Curr. Protoc. Stem Cell Biol. Chapter 1, unit 1H.1.1–1H.1.9 (2008).
  • Soundararajan P, Miles GB, Rubin LL, Brownstone RM, Rafuse VF. Motoneurons derived from embryonic stem cells express transcription factors and develop phenotypes characteristic of medial motor column neurons. J. Neurosci. 26(12), 3256–3268 (2006).
  • Harper JM, Krishnan C, Darman JS et al. Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. Proc. Natl Acad. Sci. USA 101(18), 7123–7128 (2004).
  • Adler S, Bicker G, Bigalke H et al. The current scientific and legal status of alternative methods to the LD50 test for botulinum neurotoxin potency testing. The report and recommendations of a ZEBET Expert Meeting. Altern. Lab. Anim. 38(4), 315–330 (2010).
  • Seok J, Warren HS, Cuenca AG et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc. Natl Acad. Sci. USA 110(9), 3507–3512 (2013).
  • McNeish J, Roach M, Hambor J et al. High-throughput screening in embryonic stem cell-derived neurons identifies potentiators of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate-type glutamate receptors. J. Biol. Chem. 285(22), 17209–17217 (2010).
  • Li XJ, Hu BY, Jones SA et al. Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules. Stem Cells 26(4), 886–893 (2008).
  • Hu BY, Zhang SC. Directed differentiation of neural-stem cells and subtype-specific neurons from hESCs. Methods Mol. Biol. 636, 123–137 (2009).
  • Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell 3(6), 637–648 (2008).
  • Dimos JT, Rodolfa KT, Niakan KK et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893), 1218–1221 (2008).
  • Lee H, Shamy GA, Elkabetz Y et al. Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells 25(8), 1931–1939 (2007).
  • Singh Roy N, Nakano T, Xuing L et al. Enhancer-specified GFP-based FACS purification of human spinal motor neurons from embryonic stem cells. Exp. Neurol. 196(2), 224–234 (2005).
  • Nizzardo M, Simone C, Falcone M et al. Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells. Cell. Mol. Life Sci. 67(22), 3837–3847 (2010).
  • Amoroso MW, Croft GF, Williams DJ et al. Accelerated high-yield generation of limb-innervating motor neurons from human stem cells. J. Neurosci. 33(2), 574–586 (2013).
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663–676 (2006).
  • Marchetto MC, Brennand KJ, Boyer LF, Gage FH. Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Hum. Mol. Genet. 20(R2), R109–R115 (2011).
  • Boland MJ, Hazen JL, Nazor KL et al. Adult mice generated from induced pluripotent stem cells. Nature 461(7260), 91–94 (2009).
  • Zhao XY, Li W, Lv Z et al. Viable fertile mice generated from fully pluripotent iPS cells derived from adult somatic cells. Stem Cell Rev. 6(3), 390–397 (2010).
  • Narsinh KH, Plews J, Wu JC. Comparison of human induced pluripotent and embryonic stem cells: fraternal or identical twins? Mol. Ther. 19(4), 635–638 (2011).
  • Hu BY, Weick JP, Yu J et al. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc. Natl Acad. Sci. USA 107(9), 4335–4340 (2010).
  • Feng Q, Lu SJ, Klimanskaya I et al. Hemangioblastic derivatives from human induced pluripotent stem cells exhibit limited expansion and early senescence. Stem Cells 28(4), 704–712 (2010).
  • Narsinh KH, Sun N, Sanchez-Freire V et al. Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells. J. Clin. Invest. 121(3), 1217–1221 (2011).
  • Sandoe J, Eggan K. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. Nat. Neurosci. 16(7), 780–789 (2013).
  • Bar-Nur O, Russ HA, Efrat S, Benvenisty N. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9(1), 17–23 (2011).
  • Bock C, Kiskinis E, Verstappen G et al. Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144(3), 439–452 (2011).
  • Lister R, Pelizzola M, Kida YS et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471(7336), 68–73 (2011).
  • Boulting GL, Kiskinis E, Croft GF et al. A functionally characterized test set of human induced pluripotent stem cells. Nat. Biotechnol. 29(3), 279–286 (2011).
  • Marchetto MC, Muotri AR, Mu Y et al. Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell 3(6), 649–657 (2008).
  • Yang N, Ng YH, Pang ZP, Sudhof TC, Wernig M. Induced neuronal cells: how to make and define a neuron. Cell Stem Cell 9(6), 517–525 (2011).
  • Son EY, Ichida JK, Wainger BJ et al. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9(3), 205–218 (2011).
  • Zhang Y, Pak C, Han Y et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78(5), 785–798 (2013).
  • Buchser W, Collins M, Garyantes T et al. Assay development guidelines for image-based high content screening, high content analysis and high content imagingM. In: Assay Guidance Manual. Sittampalam GS, Gal-Edd N, Arkin M et al. (Eds). Bethesda, MD, USA (2004)
  • Eglen RM, Reisine T. New insights into GPCR function: implications for HTS. Methods Mol. Biol. 552, 1–13 (2009).
  • de Paiva A, Meunier FA, Molgo J, Aoki KR, Dolly JO. Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc. Natl Acad. Sci. USA 96(6), 3200–3205 (1999).
  • Bickle M. The beautiful cell: high-content screening in drug discovery. Anal. Bioanal. Chem. 398(1), 219–226 (2010).
  • Honer WG, Falkai P, Bayer TA et al. Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness. Cereb. Cortex 12(4), 349–356 (2002).
  • Degorce F, Card A, Soh S et al. HTRF: a technology tailored for drug discovery - a review of theoretical aspects and recent applications. Curr. Chem. Genomics 3, 22–32 (2009).
  • Bakry N, Kamata Y, Simpson LL. Lectins from triticum vulgaris and limax flavus are universal antagonists of botulinum neurotoxin and tetanus toxin. J. Pharmacol. Exp. Ther. 258(3), 830–836 (1991).
  • Fischer A, Nakai Y, Eubanks LM et al. Bimodal modulation of the botulinum neurotoxin protein-conducting channel. Proc. Natl Acad. Sci. USA 106(5), 1330–1335 (2009).

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