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Discovery of amyloid-beta aggregation inhibitors using an engineered assay for intracellular protein folding and solubility

  1. Li Ling Lee1,
  2. HyungHo Ha2,
  3. Young-Tae Chang2,
  4. Matthew P. DeLisa1,3,*

Article first published online: 15 DEC 2008

DOI: 10.1002/pro.33

Issue

Protein Science

Protein Science

Volume 18, Issue 2, pages 277–286, February 2009

Additional Information

How to Cite

Lee, L. L., Ha, H., Chang, Y.-T. and DeLisa, M. P. (2009), Discovery of amyloid-beta aggregation inhibitors using an engineered assay for intracellular protein folding and solubility. Protein Science, 18: 277–286. doi: 10.1002/pro.33

Author Information

  1. 1

    School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853

  2. 2

    Department of Chemistry, National University of Singapore, Singapore 117543

  3. 3

    Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853

*School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853

Publication History

  1. Issue published online: 30 JAN 2009
  2. Article first published online: 15 DEC 2008
  3. Accepted manuscript online: 15 DEC 2008 12:00AM EST
  4. Manuscript Accepted: 9 NOV 2008
  5. Manuscript Revised: 8 NOV 2008
  6. Manuscript Received: 5 SEP 2008

Funded by

  • Alzheimer's Association. Grant Number: NIRG-06-26626
  • National Institutes of Health. Grant Number: 1R21NS056911-01
  • NSF CAREER Award. Grant Number: BES #0449080

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References

  • 1
    Selkoe DJ, Schenk D ( 2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43: 545–584.
  • 2
    Hardy JA, Higgins GA ( 1992) Alzheimer's disease: the amyloid cascade hypothesis. Science 256: 184–185.
  • 3
    Hardy J, Selkoe DJ ( 2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297: 353–356.
  • 4
    Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL ( 1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA 95: 6448–6453.
  • 5
    Aisen PS ( 2005) The development of anti-amyloid therapy for Alzheimer's disease: from secretase modulators to polymerisation inhibitors. CNS Drugs 19: 989–996.
  • 6
    Aisen PS, Gauthier S, Vellas B, Briand R, Saumier D, Laurin J, Garceau D ( 2007) Alzhemed: a potential treatment for Alzheimer's disease. Curr Alzheimer Res 4: 473–478.
  • 7
    Barten, DM, Albright CF ( 2008) Therapeutic strategies for Alzheimer's Disease. Mol Neurobiol 37: 171–186.
  • 8
    Wolfe MS ( 2008) Gamma-secretase inhibition and modulation for Alzheimer's disease. Curr Alzheimer Res 5: 158–164.
  • 9
    Wood SJ, MacKenzie L, Maleeff B, Hurle MR, Wetzel R ( 1996) Selective inhibition of Abeta fibril formation. J Biol Chem 271: 4086–4092.
  • 10
    Esler WP, Stimson ER, Ghilardi JR, Felix AM, Lu YA, Vinters HV, Mantyh PW, Maggio JE ( 1997) Abeta deposition inhibitor screen using synthetic amyloid. Nat Biotechnol 15: 258–263.
  • 11
    Lansbury PT, Jr ( 1997) Inhibition of amyloid formation: a strategy to delay the onset of Alzheimer's disease. Curr Opin Chem Biol 1: 260–267.
  • 12
    Blanchard BJ, Chen A, Rozeboom LM, Stafford KA, Weigele P, Ingram VM ( 2004) Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule. Proc Natl Acad Sci USA 101: 14326–14332.
  • 13
    Hartley DM, Walsh DM, Ye CP, Diehl T, Vasquez S, Vassilev PM, Teplow DB, Selkoe DJ ( 1999) Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci 19: 8876–8884.
  • 14
    Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ ( 2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535–539.
  • 15
    Walsh DM, Selkoe DJ ( 2004) Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration. Protein Pept Lett 11: 213–228.
  • 16
    Fisher AC, Kim W, DeLisa MP ( 2006) Genetic selection for protein solubility enabled by the folding quality control feature of the twin-arginine translocation pathway. Protein Sci 15: 449–458.
    Direct Link:
  • 17
    Wurth C, Guimard NK, Hecht MH ( 2002) Mutations that reduce aggregation of the Alzheimer's Abeta42 peptide: an unbiased search for the sequence determinants of Abeta amyloidogenesis. J Mol Biol 319: 1279–1290.
  • 18
    Zlokarnik G, Negulescu PA, Knapp TE, Mere L, Burres N, Feng L, Whitney M, Roemer K, Tsien RY ( 1998) Quantitation of transcription and clonal selection of single living cells with beta-lactamase as reporter. Science 279: 84–88.
  • 19
    Nord O, Gustrin A, Nygren PA ( 2005) Fluorescent detection of beta-lactamase activity in living Escherichia coli cells via esterase supplementation. FEMS Microbiol Lett 242: 73–79.
    Direct Link:
  • 20
    Zhang JH, Chung TD, Oldenburg KR ( 1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4: 67–73.
  • 21
    Bork JT, Lee J, Chang YT ( 2003) Palladium-catalyzed cross-coupling reaction of resin bound chlorotriazines. Tetrahedron Lett 44: 6141–6144.
  • 22
    Khersonsky SM, Jung DW, Kang TW, Walsh DP, Moon HS, Jo H, Jacobson EM, Shetty V, Neubert TA Chang YT ( 2003) Facilitated forward chemical genetics using a tagged triazine library and zebrafish embryo screening. J Am Chem Soc 125: 11804–11805.
  • 23
    Kim W, Kim Y, Min J, Kim DJ, Chang YT, Hecht MH ( 2006) A high-throughput screen for compounds that inhibit aggregation of the Alzheimer's peptide. ACS Chem Biol 1: 461–469.
  • 24
    Walsh DM, Townsend M, Podlisny MB, Shankar GM, Fadeeva JV, El Agnaf O, Hartley DM, Selkoe DJ ( 2005) Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation. J Neurosci 25: 2455–2462.
  • 25
    Bitan G, Teplow DB ( 2005) Preparation of aggregate-free, low molecular weight amyloid-beta for assembly and toxicity assays. Methods Mol Biol 299: 3–9.
  • 26
    LeVine H, III ( 1993) Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci 2: 404–410.
    Direct Link:
  • 27
    Ono K, Hasegawa K, Naiki H, Yamada M ( 2004) Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res 75: 742–750.
    Direct Link:
  • 28
    Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM ( 2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280: 5892–5901.
  • 29
    Ono K, Hirohata M, Yamada M ( 2005) Ferulic acid destabilizes preformed beta-amyloid fibrils in vitro. Biochem Biophys Res Commun 336: 444–449.
  • 30
    Ono K, Hasegawa K, Naiki H, Yamada M ( 2004) Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimer's beta-amyloid fibrils in vitro. Biochim Biophys Acta 1690: 193–202.
  • 31
    Byeon SR, Lee JH, Sohn JH, Kim DC, Shin KJ, Yoo KH, Mook-Jung I, Lee WK, Kim DJ ( 2007) Bis-styrylpyridine and bis-styrylbenzene derivatives as inhibitors for Abeta fibril formation. Bioorg Med Chem Lett 17: 1466–1470.
  • 32
    Moore SA, Huckerby TN, Gibson GL, Fullwood NJ, Turnbull S, Tabner BJ, El-Agnaf OM, Allsop D ( 2004) Both the D-(+) and L-(−) enantiomers of nicotine inhibit Abeta aggregation and cytotoxicity. Biochemistry 43: 819–826.
  • 33
    Nakagami Y, Nishimura S, Murasugi T, Kaneko I, Meguro M, Marumoto S, Kogen H, Koyama K, Oda T ( 2002) A novel beta-sheet breaker, RS-0406, reverses amyloid beta-induced cytotoxicity and impairment of long-term potentiation in vitro. Br J Pharmacol 137: 676–682.
    Direct Link:
  • 34
    Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, Greenfield JP, Haroutunian V, Buxbaum JD, Xu H, Greengard P, Relkin NR. ( 2000) Intraneuronal Abeta42 accumulation in human brain. Am J Pathol 156: 15–20.
  • 35
    Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ ( 2000) The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. Biochemistry 39: 10831–10839.
  • 36
    D'Andrea MR, Nagele RG, Wang HY, Peterson PA, Lee DH ( 2001) Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease. Histopathology 38: 120–134.
    Direct Link:
  • 37
    Echeverria V, Cuello AC ( 2002) Intracellular A-beta amyloid, a sign for worse things to come? Mol Neurobiol 26: 299–316.
  • 38
    Tabira T, Chui DH, Kuroda S ( 2002) Significance of intracellular Abeta42 accumulation in Alzheimer's disease. Front Biosci 7: a44–a49.
  • 39
    Takahashi RH, Almeida CG, Kearney PF, Yu F, Lin MT, Milner TA, Gouras GK ( 2004) Oligomerization of Alzheimer's beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci 24: 3592–3599.
  • 40
    Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ. ( 2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14: 837–842.
  • 41
    Gohlke U, Pullan L, McDevitt CA, Porcelli I, de Leeuw E, Palmer T, Saibil HR, Berks BC ( 2005) The TatA component of the twin-arginine protein transport system forms channel complexes of variable diameter. Proc Natl Acad Sci USA 102: 10482–10486.
  • 42
    Skretas G, Meligova AK, Villalonga-Barber C, Mitsiou DJ, Alexis MN, Micha-Screttas M, Steele BR, Screttas CG, Wood DW ( 2007) Engineered chimeric enzymes as tools for drug discovery: generating reliable bacterial screens for the detection, discovery, and assessment of estrogen receptor modulators. J Am Chem Soc 129: 8443–8457.
  • 43
    Melnick L, Yang SS, Rossi R, Zepp C, Heefner D ( 1998) An Escherichia coli expression assay and screen for human immunodeficiency virus protease variants with decreased susceptibility to indinavir. Antimicrob Agents Chemother 42: 3256–3265.
  • 44
    Cheng TJ, Brik A, Wong CH, Kan CC ( 2004) Model system for high-throughput screening of novel human immunodeficiency virus protease inhibitors in Escherichia coli.. Antimicrob Agents Chemother 48: 2437–2447.
  • 45
    Chen G, Hayhurst A, Thomas JG, Harvey BR, Iverson BL, Georgiou G ( 2001) Isolation of high-affinity ligand-binding proteins by periplasmic expression with cytometric screening (PECS). Nat Biotechnol 19: 537–542.
  • 46
    Sroga GE, Dordick JS ( 2001) Generation of a broad esterolytic subtilisin using combined molecular evolution and periplasmic expression. Protein Eng 14: 929–937.
  • 47
    Sroga GE, Dordick JS ( 2002) A strategy for in vivo screening of subtilisin E reaction specificity in E. coli periplasm. Biotechnol Bioeng 78: 761–769.
    Direct Link:
  • 48
    Bagriantsev S, Liebman S ( 2006) Modulation of Abeta42 low-n oligomerization using a novel yeast reporter system. BMC Biol 4: 32.
  • 49
    Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H ( 2006) Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2: 20060008.
  • 50
    Guzman LM, Belin D, Carson MJ, Beckwith J ( 1995) Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol 177: 4121–4130.
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