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Bacteriophage Therapies Targets Multiple Diseases Caused by Protein Misfolding

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Biocommunication of Phages

Abstract

Filamentous bacteriophages (Ff) are a group of related viruses which infect only gram-negative bacteria They are flexible filaments of about 900 nm long and 6−10 nm thick, similar to amyloid fibrils The similarity in characteristics and conformation between amyloids that are composed of different proteins without any sequence homology raised the hypothesis that filamentous phages may affect protein amyloids regardless of the protein from which they are composed. Indeed the filamentous phages may bind to a certain conformation or region which is common for several types of amyloids and effect their aggregation similar to conformational antibodies.

Moreover the filamentous bacteriophage proved to be an efficient and non-toxic viral delivery vector of antibodies to the brain, following the olfactory tract and an efficient immunocarrier for raising antibodies. The therapeutic potential of phages in amyloidogenic diseases, stems from their unprecedented ability to access the CNS, to induce a potent anti-aggregating effect, and from their lack of tropism to mammalian cells.

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References

  • Banks WA, Terrell B, Farr SA, Robinson S, Nonaka N, Morley E (2002) Passage of amyloid beta protein antibody across the blood-brain barrier in a mouse model of Alzheimer’s disease. Peptides 23:2223–2226

    CAS  PubMed  Google Scholar 

  • Bard F, Barbour R, Cannon C, Carretto R, Games D, Guido T, Hoenow K, Hu K, Johnson-Wood K, Khan K, Kholodenko LC, Lee M, Motter R, Nguyen M, Reed A, Schenk D, Tang P, Vasquez N, Seubert P, Yednock T (2000) Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimer’s disease-like neuropathology. Proc Natl Acad Sci U S A 100:2023–2028

    Google Scholar 

  • Dabrowska K, Switala-Jelen K, Opolski A, Weber-Dabrowska B, Gorski A (2005) Bacteriophage penetration in vertebrates. J Appl Microbiol 98:7–13

    CAS  PubMed  Google Scholar 

  • Delmastro P, Meola A, Monaci P, Cortese R, Galfre G (1997) Immunogenicity of filamentous phage displaying peptide mimotopes after oral administration. Vaccine 15:1276–1285

    CAS  PubMed  Google Scholar 

  • Dickerson TJ, Janda KD (2005) Recent advances for the treatment of cocaine abuse: central nervous system Immunopharmacotherapy. AAPS J 7:E579–E586

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dimant H, Solomon B (2010) Filamentous phages reduce α-Synuclein Oligomerization in the membrane fraction of SH-SY5Y cells. Neurodegener Dis 7:203–205

    CAS  PubMed  Google Scholar 

  • Dimant H, Sharon N, Solomon B (2009) Modulation effect of filamentous phage on a-synuclein aggregation Biochem. Biophys Res Comm 383:491–496

    CAS  Google Scholar 

  • Dobson CM (1999) Protein misfolding, evolution and disease. Trends Biochem Sci 24:329–332

    CAS  PubMed  Google Scholar 

  • El-Agnaf SA, Salem KE, Paleologou MD, Curran MJ, Gibson JA, Court MG, Schlossmacher MG, Allsop D (2006) Detection of oligomeric forms of {alpha}-synuclein protein in human plasma as a potential biomarker for Parkinson’s disease. FASEB J 20:419–425

    CAS  PubMed  Google Scholar 

  • Frenkel D, Solomon B (2002) Filamentous phage as vector-mediated antibody delivery to the brain. Proc Natl Acad Sci U S A 99:5675–5679

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frenkel D, Balass M, Solomon B (1998) N-Terminal EFRH sequence of Alzheimer’s β-amyloid peptide represents the epitope of its anti-aggregating antibodies. J Neuroimmunol 88:85–90

    CAS  PubMed  Google Scholar 

  • Frenkel D, Dewachter I, Van Leuven F, Solomon B (2003) Reduction of beta-amyloid plaques in brain of transgenic mouse model of Alzheimer’s disease by EFRH-phage immunization. Vaccine 7:1060–1065

    Google Scholar 

  • Frey WI (2002) Bypassing the blood-brain barrier to deliver therapeutic agents to the brain and spinal cord. Drug Delivery Technol 2:46–49

    Google Scholar 

  • Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T et al (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373:523–527

    CAS  PubMed  Google Scholar 

  • Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2:492–501

    CAS  PubMed  Google Scholar 

  • Goren O (2008) PhD thesis Submitted to Tel Aviv University

    Google Scholar 

  • Griffith J, Manning M, Dunn K (1981) Filamentous bacteriophage contract into hollow spherical particles upon exposure to a chloroform-water interface. Cell 23:747–753

    CAS  PubMed  Google Scholar 

  • Hart AM, Knight RP, Harbottle A, Mistry HD, Hunger DF, Cutler R, Williamson R, Coutelle C (1994) Cell binding and internalization by filamentous phage displaying a cyclic Arg-Gly-Asp-containing peptide. J Biol Chem 269:12468–12474

    CAS  PubMed  Google Scholar 

  • Hartman RE, Izumi Y, Bales KR, Paul SM, Wozniak DF, Holtzman DM (2005) Treatment with an amyloid-beta antibody ameliorates plaque load, learning deficits, and hippocampal long-term potentiation in a mouse model of Alzheimer’s disease. J Neurosci 25:6213–6220

    CAS  PubMed  PubMed Central  Google Scholar 

  • Illum L (2000) Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci 11:1–18

    CAS  PubMed  Google Scholar 

  • Illum L (2002) Nasal drug delivery: new developments and strategies. Drug Discov Today 7:1184–1189

    CAS  PubMed  Google Scholar 

  • Jin K, Xie L, Childs J, Sun Y, Mao XO, Logvinova A, Greenberg DA (2003) Cerebral neurogenesis is induced by intranasal administration of growth factors. Ann Neurol 53:405–409

    CAS  PubMed  Google Scholar 

  • Kayed R, Canto I, Breydo L, Rasool S, Lukacsovich T, Wu J, Albay R 3rd, Pensalfini A, Yeung S, Head E, March JL, Glabe CG (2010) Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Abeta oligomers. Mol Neurodegener 5:57. https://doi.org/10.1186/1750-1326-5-57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krag DN, Fuller SP, Oligino L, Pero SC, Weaver D, Soden AL, Hebert C, Mills LC, Peterson D (2002) Phage-displayed random peptide libraries in mice: toxicity after serial panning. Cancer Chemother Pharmacol 50:325–332

    CAS  PubMed  Google Scholar 

  • Krishnan R, Tsubery H, Proschitsky MY, Asp E, Lulu M, Gilead S, Gartner M, Waltho JP, Davis PJ, Hounslow AM, Kirschner DA, Inouye H, Myszka DG, Wright J, Solomon B, Fisher RA (2014) A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies. J Mol Biol 426:2500–2519

    CAS  PubMed  Google Scholar 

  • Manoutcharian K, Gevorkian G, Cano A, Almagro JC (2001) Phage displated biomolecules as preventive and therapeutics agents. Curr Pharm Biotechnol 2:217–223

    CAS  PubMed  Google Scholar 

  • Marvin DA (1998) Filamentous phage structure, infection and assembly. Curr Opin Struct Biol 8:150–158

    CAS  PubMed  Google Scholar 

  • Marvin D, Hohn B (1969) Filamentous bacterial viruses. Bacteriol Rev 33:172–209

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marvin D, Pigram W, Wiseman R, Wachtel E, Marvin F (1974) Filamentous bacterial viruses. XII. Molecular architecture of the class I (fd, Ifi, Ike) virion. J Mol Biol 88:581–598

    CAS  PubMed  Google Scholar 

  • McCafferty J, Griffiths AD, Winter G, Chiswell D (1990) Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348:552–554

    CAS  PubMed  Google Scholar 

  • Meola A, Delmastro P, Monaci P, Luzzago A, Nicosia A, Felici F, Cortese R, Galfre G (1995) Derivation of vaccines from mimotopes. Immunological properties of human hepatitis virus surface antigen mimotopes displayed on filamentous phage. J Immunol 154:3162–3172

    CAS  PubMed  Google Scholar 

  • Molenaar TJ, Michon T, de Haas SA, van Berkel TJ, Kuiper J, Biessen EA (2002) Uptake and processing of modified bacteriophage M13 in mice: implications for phage display. Virology 293:182–191

    CAS  PubMed  Google Scholar 

  • Newman J, Swinney H, Day L (1977) Hydrodynamic properties and structure of fd virus. J Mol Biol 116:593–606

    CAS  PubMed  Google Scholar 

  • Opella SJ, Cross T, Di Verdi J, Sturm C (1980) Nuclear magnetic resonance of the filamentous bacteriophage fd. Biophys J 32:531–548

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pasqualini R, Ruoslahti E (1996) Organ targeting in vivo using phage display peptide libraries. Nature 380:364–366

    CAS  PubMed  Google Scholar 

  • Peters JM, Hummel T, Kratzsch T, Lotsch J, Skarke C, Frolich L (2003) Olfactory function in mild cognitive impairment and Alzheimer’s disease: an investigation using psychophysical and electrophysiological techniques. Am J Psychiatry 160:1995–2002

    PubMed  Google Scholar 

  • Rodi DJ, Makowski L (1998) Phage-display technology finding a needle I in a vast molecular haystack. Curr Opin Biotechnol 10:87–93

    Google Scholar 

  • Rossomando E, Zinder N (1968) Studies on the bacteriophage flI. Alkali-induced disassembly of the phage into DNA and protein. J Mol Biol 36:387–399

    CAS  PubMed  Google Scholar 

  • Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khon K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–177

    CAS  PubMed  Google Scholar 

  • Scott JK, Smith GP (1990) Searching for peptide ligands with an epitope library. Science 249:386–390

    CAS  PubMed  Google Scholar 

  • Selkoe DJ (1991) The molecular pathology of Alzheimer’s disease. Neuron 6:487–498

    CAS  PubMed  Google Scholar 

  • Sigurdsson P, Thorvaldsson T, Gizurarson S, Gunnarsson E (1997) Olfactory absorption of insulin to the brain. Drug Deliv 4:195–200

    CAS  Google Scholar 

  • Smith GP (1985) Filamentous fusion phage; novel expression vectors that display cloned antigens on the virion surface. Science 228:1315–1317

    CAS  PubMed  Google Scholar 

  • Smith HW, Huggins RB (1982) Successful treatment of experimental E coli infections in mice using phage: its general superiority over antibiotics. J Gen Microbiol 128:307–318

    CAS  PubMed  Google Scholar 

  • Solomon B, Koppel R, Hanan E, Katzav T (1996) Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer beta-amyloid peptide. Proc Natl Acad Sci U S A 93:452–455

    CAS  PubMed  PubMed Central  Google Scholar 

  • Solomon B, Koppel R, Frankel D, Hanan-Aharon E (1997) Disaggregation of Alzheimer beta-amyloid by site-directed mAb. Proc Natl Acad Sci U S A 94:4109–4112

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soto C, Estrada L, Castilla J (2006) Amyloids, prions and the inherent infectious nature of misfolded protein aggregates. Trends Biochem Sci 31:150–155

    CAS  PubMed  Google Scholar 

  • Stone R (2002) Stalin’s forgotten cure. Science 298:728–731

    CAS  PubMed  Google Scholar 

  • Thorne RG, Frey WH (2001) Delivery of neurotrophic factors to the central nervous system: pharmacokinetic considerations. Clin Pharmacokinet 40:907–946

    CAS  PubMed  Google Scholar 

  • Vasilevko V, Cribbs DH (2006) Novel approaches for immunotherapeutic intervention in Alzheimer’s disease. Neurochem Int 49:113–126

    CAS  PubMed  Google Scholar 

  • Weksler ME, Gouras G, Relkin NR, Szabo P (2005) The immune system, amyloid-β peptide, and Alzheimer’s disease. Immunol Rev 205:244–256

    CAS  PubMed  Google Scholar 

  • Willis EA, Perham NR, Wraaith D (1993) Immunological properties of foreign peptides in multiple display on a filamentous bacteriophage. Gene 128:79–83

    CAS  PubMed  Google Scholar 

  • Zou J, Dickerson MT, Owen NK, Landon LA, Deutscher SL (2004) Distribution of filamentous phage peptide libraries in mice Mol. Biol Reprod 31:121–129

    CAS  Google Scholar 

  • Zuercher AW, Miescher SM, Vogel M, Rudolf MR, Stadler MB, Stadler BM (2000) Oral anti-IgE immunization with epitope-displaying phage. Eur J Immunol 30:128–135

    CAS  PubMed  Google Scholar 

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Correspondence to Beka Solomon .

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Solomon, B. (2020). Bacteriophage Therapies Targets Multiple Diseases Caused by Protein Misfolding. In: Witzany, G. (eds) Biocommunication of Phages. Springer, Cham. https://doi.org/10.1007/978-3-030-45885-0_19

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