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Architecture of the Alzheimer’s AβP Ion Channel Pore

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Abstract

We have proposed that the cytotoxic action of Alzheimer’s amyloid beta protein might be initiated by the interaction with the neuronal cell membrane, and subsequent formation of toxic ion channels. Consequently, AβP toxicity can be explained on the basis of harmful ion fluxes across AβP channels. The conformation of AβP in membranes is not known. However, several models suggests that a transmembrane annular polymeric structure is responsible for the ion channel properties of the membrane-bound AβP. To identify that portion of the AβP molecule making up the conducting pore we have hypothesized that the region of the AβP sequence in the vicinity of the hypothetical pore might interact with complementary regions in the adjacent AβP subunits. We have further hypothesized that an interaction by a peptide segment would block AβP conductance. To test this hypothesis we synthesized peptides that encompass the histidine dyad (H-H) previously hypothesized to line the pore. We report here that peptides designed to most closely match the proposed pore are, in fact, the most effective at blocking ion currents through the membrane-incorporated AβP channel. As previously shown for Zn2+ blockade, peptide blockade is also asymmetric. The results also provide additional evidence for the asymmetric insertion of the AβP molecules into lipid membranes, and give support to the concept that rings of histidines line the entry to one side of the AβP pore.

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References

  1. N. Arispe (2001) ArticleTitleControl of the interaction of the Alzheimer’s AβPs and homologous analogues, with lipid membranes. Biophys. J. 80 135a

    Google Scholar 

  2. N.J. Arispe M. Doh (2003) ArticleTitlePeptides that block Alzheimer’s AβP ion channels protect cells from AβP toxicity. Biophysical J. 84 53a

    Google Scholar 

  3. N. Arispe M. Doh A. De Maio (2002) ArticleTitleLipid interactions differentiates the constitutive and stress-induced heat shock proteins Hsc70 and Hsp70. Cell Stress and Chaperones 7 330–338 Occurrence Handle1:CAS:528:DC%2BD3sXksVyluw%3D%3D Occurrence Handle12653477

    CAS  PubMed  Google Scholar 

  4. N. Arispe H.B. Pollard E. Rojas (1994) ArticleTitleβ-amyloid Ca2+-channel hypothesis for neuronal death in Alzheimer disease. Mol. Cell. Biochem. 140 19–125

    Google Scholar 

  5. N. Arispe H.B. Pollard E. Rojas (1996a) ArticleTitleZn2+ interaction with Alzheimer amyloid β protein calcium channels. Proc. Natl. Acad. Sci. USA 93 1710–1715 Occurrence Handle1:CAS:528:DyaK28Xht1entLg%3D

    CAS  Google Scholar 

  6. N. Arispe E. Rojas B.R. Gene L.N.Y. Wu R. Wuthier (1996b) ArticleTitleSimilarity in calcium channel activity of annexin V and matrix vesicles in planar lipid bilayers. Biophys. J. 71 1764–1775 Occurrence Handle1:CAS:528:DyaK28XmtVOktr4%3D

    CAS  Google Scholar 

  7. N. Arispe E. Rojas H.B. Pollard (1993a) ArticleTitleAlzheimer disease amyloid β-protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminium. Proc. Natl. Acad. Sci. USA 90 567–571 Occurrence Handle1:CAS:528:DyaK3sXpvFKitQ%3D%3D

    CAS  Google Scholar 

  8. N. Arispe E. Rojas H.B. Pollard (1993b) ArticleTitleGiant multilevel cation channels formed by Alzheimer disease amyloid β-protein [AβP-(1–40)] in bilayer membranes. Proc. Natl. Acad. Sci. USA 90 10573–10577 Occurrence Handle1:CAS:528:DyaK2cXnsVOisQ%3D%3D

    CAS  Google Scholar 

  9. N.A. Avdulov S.V. Cochina U. Igbavboa C.S. Warden A.V. Vassiliev W.G. Wood (1997) ArticleTitleLipid binding to amyloid-β-peptide aggregates. Preferential binding of cholesterol as compared with phosphatidylcholine and fatty acids. J. Neurochem. 69 1746–1752 Occurrence Handle1:CAS:528:DyaK2sXmsVCktrc%3D Occurrence Handle9326304

    CAS  PubMed  Google Scholar 

  10. C.J. Barrow A. Yasuda P.T.M. Kenny M.G. Zagorski (1992) ArticleTitleSolution conformations and aggregational properties of synthetic amyloid β-peptides of Alzheimer’s disease. Analysis of circular dichroism spectra. J. Mol. Biol. 225 1075–1093 Occurrence Handle1:CAS:528:DyaK38XltV2gs7g%3D Occurrence Handle1613791

    CAS  PubMed  Google Scholar 

  11. R. Bathia H. Lin R. Lal (2000) ArticleTitleFresh and globular amyloid-β- protein induces rapid cellular degeneration. A possible implication for calcium-uptake via AβP-channel. FASEB J. 14 1233–1243 Occurrence Handle10834945

    PubMed  Google Scholar 

  12. R.A. Blackwood J.D. Ernst (1990) ArticleTitleCharacterization of Ca2+-dependent phospholipid binding, vesicle aggregation and membrane fusion by annexins. Biochem. J. 266 195–200 Occurrence Handle1:CAS:528:DyaK3cXhtFCntLo%3D Occurrence Handle2138016

    CAS  PubMed  Google Scholar 

  13. D. Burdick B. Soreghan M. Kwon J. Kosmoski M. Knauer A. Henschen J. Yates C. Cotman C. Glabe (1992) ArticleTitleAssembly and aggregation properties of synthetic Alzheimer’s A4/beta amyloid peptide analogs. J. Biol. Chem. 267 546–554 Occurrence Handle1:CAS:528:DyaK38XjvFSmtA%3D%3D Occurrence Handle1730616

    CAS  PubMed  Google Scholar 

  14. M. de la Fuente A.V. Parra (1995) ArticleTitleVesicle aggregation by annexin I: role of a secondary membrane binding site. Biochemistry. 34 10393–10399 Occurrence Handle1:CAS:528:DyaK2MXnt1KmtLc%3D Occurrence Handle7654693

    CAS  PubMed  Google Scholar 

  15. S.R. Durrell H.R. Guy N. Arispe E. Rojas H.B. Pollard (1994) ArticleTitleTheoretical models of the ion channel structure of amyloid-β-protein. Biophys. J. 67 2137–2145 Occurrence Handle1:CAS:528:DyaK2MXisVajtL0%3D Occurrence Handle7535109

    CAS  PubMed  Google Scholar 

  16. S.P. Frazer Y.-H. Suh M.B.A. Djamgoz (1997) ArticleTitleIonic effects of the Alzheimer’s disease β-amyloid precursor protein and its metabolic fragments. Trends Neurosci. 20 67–72 Occurrence Handle10.1016/S0166-2236(96)10079-5 Occurrence Handle9023874

    Article  PubMed  Google Scholar 

  17. K. Furukawa Y. Abe N. Akaike (1994) ArticleTitleAmyloid β protein-induced irreversible current in rat cortical neurones. NeuroReport. 5 2016–2018 Occurrence Handle1:CAS:528:DyaK2MXitlKis78%3D Occurrence Handle7532452

    CAS  PubMed  Google Scholar 

  18. Z. Galdzicki R. Fukuyama K. Wadhwani S. Rapoport G. Ehrenstein (1994) ArticleTitleβ-amyloid increases choline conductance of PC12 cells: possible mechanism of toxicity in Alzheimer’s disease. Brain Res. 646 332–336 Occurrence Handle10.1016/0006-8993(94)90101-5 Occurrence Handle1:CAS:528:DyaK2cXksFGis7Y%3D Occurrence Handle8069685

    Article  CAS  PubMed  Google Scholar 

  19. J. Ghanta C.-L. Shen L.L. Kiessling R.M. Murphy (1996) ArticleTitleA strategy for designing inhibitors of β-amyloid toxicity. J. Biol. Chem. 271 29525–29528 Occurrence Handle10.1074/jbc.271.47.29525 Occurrence Handle1:CAS:528:DyaK28XntFKmsrw%3D Occurrence Handle8939877

    Article  CAS  PubMed  Google Scholar 

  20. G.G. Glenner C.W. Wong (1984) ArticleTitleAlzheimer’s Disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Comm. 120 885–890 Occurrence Handle1:CAS:528:DyaL2cXitVOntLw%3D Occurrence Handle6375662

    CAS  PubMed  Google Scholar 

  21. C. Haass M. Schlossmacher A.Y. Hung et al. (1992) ArticleTitleAmyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359 322–325 Occurrence Handle10.1038/359322a0 Occurrence Handle1:CAS:528:DyaK38XmtV2msro%3D Occurrence Handle1383826

    Article  CAS  PubMed  Google Scholar 

  22. C. Haass D.J. Selkoe (1993) ArticleTitleCellular processing of β-amyloid precursor protein and the genesis of amyloid-β-peptide. Cell 75 1039–1042 Occurrence Handle1:CAS:528:DyaK2cXnsVeksQ%3D%3D Occurrence Handle8261505

    CAS  PubMed  Google Scholar 

  23. J.A. Hardy G.A. Higgins (1992) ArticleTitleAlzheimer’s disease: the amyloid cascade hypothesis. Science 256 780–783 Occurrence Handle1589757

    PubMed  Google Scholar 

  24. Y. Hirakura M.C. Lin B.L. Kagan (1999) ArticleTitleAlzheimer amyloid beta peptide 1-42 channels: effect of solvent, pH, and congo red. J. Neurosci. Res. 57 458–460 Occurrence Handle10.1002/(SICI)1097-4547(19990815)57:4<458::AID-JNR5>3.3.CO;2-W Occurrence Handle1:CAS:528:DyaK1MXltFWmtbk%3D Occurrence Handle10440895

    Article  CAS  PubMed  Google Scholar 

  25. Y. Hirakura W.W. Yiu A. Yamamoto B.L. Kagan (2000) ArticleTitleAmyloid peptide channels: blockade by zinc and inhibition by Congo red. Amyloid 7 194–199 Occurrence Handle1:CAS:528:DC%2BD3cXnsFCqtrg%3D Occurrence Handle11019860

    CAS  PubMed  Google Scholar 

  26. M. Kawahara N. Arispe Y. Kuroda E. Rojas (1997) ArticleTitleAlzheimer’s disease amyloid β-protein forms Zn2+-sensitive cation-selective channels across excited membrane patches from hypothalamic neurons. Biophysical J. 73 67–75 Occurrence Handle1:CAS:528:DyaK2sXktlaksLo%3D

    CAS  Google Scholar 

  27. N.C. Kowall A.C. McKee B.A. Yankner M.F. Beal (1992) ArticleTitleIn vivo neurotoxicity of beta amyloid [β(1–40)] and thte β(25–35) fragment. Neurobiol. of Aging 13 531–542 Occurrence Handle10.1016/0197-4580(92)90083-A

    Article  Google Scholar 

  28. K.Y.C. Lee (2001) ArticleTitleInteractions of Alzheimer’s amyloid-beta-peptides with lipid membranes. Biophys. J. 80 23a

    Google Scholar 

  29. G. Lee H.B. Pollard (1997) ArticleTitleHighly sensitive and stable phosphatidylserine liposome aggregation assay for annexins. Analyt. Biochem. 252 160–164 Occurrence Handle10.1006/abio.1997.2311 Occurrence Handle1:CAS:528:DyaK2sXmsVWrs7Y%3D Occurrence Handle9324954

    Article  CAS  PubMed  Google Scholar 

  30. H. Lin R. Bhatia R. Lal (2001) ArticleTitleAmyloid protein forms ion channels: implications for Alzheimer’s disease pathophysiology. FASEB J. 15 2433–2444 Occurrence Handle10.1096/fj.01-0377com Occurrence Handle1:CAS:528:DC%2BD3MXoslSisrs%3D Occurrence Handle11689468

    Article  CAS  PubMed  Google Scholar 

  31. H. Lin Y.J. Zhu R. Lal (1999) ArticleTitleAmyloid β-protein (1–40) forms calcium-permeable Zn2+ sensitive channels in reconstituted lipid vesicles. Biochemistry 38 11189–11196 Occurrence Handle1:CAS:528:DyaK1MXkvVCrsro%3D Occurrence Handle10460176

    CAS  PubMed  Google Scholar 

  32. M.C. Lin B. Kagan (2002) ArticleTitleElectrophysiologic properties of channels induced by Aβ25–35 in planar lipid bilayers. Peptides 23 1215–1228 Occurrence Handle10.1016/S0196-9781(02)00057-8 Occurrence Handle1:CAS:528:DC%2BD38XlsVOqt7c%3D Occurrence Handle12128079

    Article  CAS  PubMed  Google Scholar 

  33. A.T. Maloof (1992) ArticleTitleEffect of beta amyloid peptides on neurons in hippocampal slice cultures. Neurobiol. of Aging 13 543–551 Occurrence Handle10.1016/0197-4580(92)90054-2

    Article  Google Scholar 

  34. R.P. Mason J.D. Estermyer J.F. Kelly P.E. Mason (1996) ArticleTitleAlzheimer’s disease amyloid β peptide 25–35 is localized in the membrane hydrocarbon core: X-ray diffration analysis. Biochem. Biophys. Res. Comm. 222 78–82 Occurrence Handle10.1006/bbrc.1996.0699 Occurrence Handle1:CAS:528:DyaK28XivVOitro%3D Occurrence Handle8630078

    Article  CAS  PubMed  Google Scholar 

  35. C.L. Masters G. Simms N.A. Weinman G. Multhaup B.L. McDonald K. Beyreuther (1985) ArticleTitleAmyloid plaque core protein in Alzheimer’s disease and Down syndrome. Proc. Natl Acad. Sci. USA 82 4245–4249 Occurrence Handle1:CAS:528:DyaL2MXktlGltr0%3D Occurrence Handle3159021

    CAS  PubMed  Google Scholar 

  36. M.P. Mattson (1997) ArticleTitleCellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev. 77 1081–1132 Occurrence Handle1:CAS:528:DyaK2sXnt1yhu7g%3D Occurrence Handle9354812

    CAS  PubMed  Google Scholar 

  37. M.P. Mattson B. Cheng D. Davis K. Bryant I. Liberberg R.E. Rydel (1992) ArticleTitleβ-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitoxicity. J. Neurosci. 12 376–389 Occurrence Handle1:CAS:528:DyaK38XhvFajs74%3D Occurrence Handle1346802

    CAS  PubMed  Google Scholar 

  38. T. Mirzabekov M.C. Lin W.L. Yuan P.J. Marshall M. Carman K. Tomaselli I. Lieberburg B.L. Kagan (1994) ArticleTitleChannel formation in planar lipid bilayers by a neurotoxic fragment of the beta-amyloid peptide. Biochem. Biophys. Res. Commun. 202 1142–1148 Occurrence Handle10.1006/bbrc.1994.2047 Occurrence Handle1:CAS:528:DyaK2cXmt1ekurY%3D Occurrence Handle7519420

    Article  CAS  PubMed  Google Scholar 

  39. W.E. Muller S. Koch A. Eckert H. Hartmann K. Scheuer (1995) ArticleTitleβ-amyloid peptide decreases membrane fluidity. Brain Res. 674 133–136 Occurrence Handle10.1016/0006-8993(94)01463-R Occurrence Handle1:STN:280:ByqB1M7ps1c%3D Occurrence Handle7773681

    Article  CAS  PubMed  Google Scholar 

  40. R.L. Neve L.R. Dawes B.A. Yankner L.L. Benewitz W. Rodriguez G.A. Higgins (1990) ArticleTitleGenetics and biology of the Alzheimer’s amyloid precursor. Prog. Brain. Res. 86 257–267 Occurrence Handle1:CAS:528:DyaK3MXltFWltrw%3D Occurrence Handle2150887

    CAS  PubMed  Google Scholar 

  41. C.J. Pike M.J. Overman C.W. Cotman (1995) ArticleTitleAmino-terminal deletions enhance aggregation of amyloid peptides in vitro. J. Biol Chem. 270 23895–23898 Occurrence Handle10.1074/jbc.270.41.23895 Occurrence Handle1:CAS:528:DyaK2MXovVSgsL4%3D Occurrence Handle7592576

    Article  CAS  PubMed  Google Scholar 

  42. C.J. Pike A.J. Walencewicz C.G. Glabe C.W. Cottman (1991) ArticleTitleIn vitro aging of β-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res. 563 311–314 Occurrence Handle10.1016/0006-8993(91)91553-D Occurrence Handle1:CAS:528:DyaK38Xks1al Occurrence Handle1786545

    Article  CAS  PubMed  Google Scholar 

  43. J.F. Poduslo G.L. Curran A. Kumar B. Frangione C. Soto (1999) ArticleTitleBeta-sheet breaker peptide inhibitor of Alzheimer’s amyloidogenesis with increased blood-brain barrier permeability and resistance to proteolytic degradation in plasma. J. Neurobiol. 39 371–382 Occurrence Handle10.1002/(SICI)1097-4695(19990605)39:3<371::AID-NEU4>3.3.CO;2-5 Occurrence Handle1:CAS:528:DyaK1MXjvVCmsr4%3D Occurrence Handle10363910

    Article  CAS  PubMed  Google Scholar 

  44. S.K. Rhee A.P. Quist R. Lal (1998) ArticleTitleAmyloid β-protein (1–42) forms calcium-permeable Zn2+-sensitive channels. J. Biol. Chem 273 13379–13382 Occurrence Handle10.1074/jbc.273.22.13379 Occurrence Handle1:CAS:528:DyaK1cXjvVejsLY%3D Occurrence Handle9593665

    Article  CAS  PubMed  Google Scholar 

  45. D. Scheuner C. Eckman M. Jensen X. Song M. Citron N. Suzuki T.D. Bird J. Hardy M. Hutton W. Kukull E. Larson E. Levy-Lahad M. Vitanen E. Peskind P. Poorkaj G. Schellenberg R. Tanzi W. Wasco L. Lannfelt D. Selkoe S. Younkin (1996) ArticleTitleSecreted amyloid β-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat. Med. 2 864–870 Occurrence Handle1:CAS:528:DyaK28XkslGiu7g%3D Occurrence Handle8705854

    CAS  PubMed  Google Scholar 

  46. D.E. Schmechel A.M. Saunders W.S. Strittmatter B.J. Grain C.M. Hulette S.H. Joo et al. (1993) ArticleTitleIncreased amyloid beta-peptide deposition in cerebral cortex as a consequence of apoliprotein E genotype in late-onset Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 90 9646–9653

    Google Scholar 

  47. D.L. Selkoe (1991) ArticleTitleThe molecular pathology of Alzheimer’s disease. Neuron 6 487–498 Occurrence Handle1:CAS:528:DyaK3MXltlartrk%3D Occurrence Handle1673054

    CAS  PubMed  Google Scholar 

  48. D.L. Selkoe (1994) ArticleTitleAlzheimer’s disease: a central role for amyloid. J. Neuropath. Exp. Neurol. 53 438–447 Occurrence Handle1:CAS:528:DyaK2cXmsFamsbk%3D Occurrence Handle8083687

    CAS  PubMed  Google Scholar 

  49. M.A. Simmons C.R. Schneider (1993) ArticleTitleAmyloid β peptides act directly on single neurons. Neurosci. Letts. 150 133–136 Occurrence Handle10.1016/0304-3940(93)90519-Q Occurrence Handle1:CAS:528:DyaK3sXks12mtLc%3D

    Article  CAS  Google Scholar 

  50. C. Soto M.S. Kindy M. Baumann B. Frangione (1996) ArticleTitleInhibition of Alzheimer’s amyloidosis by peptides that prevent β-sheet conformation. Biochem. Biophys. Res. Comm. 226 672–680 Occurrence Handle10.1006/bbrc.1996.1413 Occurrence Handle1:CAS:528:DyaK28XlvFagsbg%3D Occurrence Handle8831674

    Article  CAS  PubMed  Google Scholar 

  51. C. Soto E.M. Sigurdsson L. Morelli R.A. Kumar E.M. Castano B. Frangione (1998) ArticleTitleBeta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer’s therapy. Nat. Med. 4 822–826 Occurrence Handle1:CAS:528:DyaK1cXktlKnsrg%3D Occurrence Handle9662374

    CAS  PubMed  Google Scholar 

  52. C. Soto G.P. Saborio B. Permanne (2000) ArticleTitleInhibiting the conversion of soluble amyloid-beta peptide into abnormally folded amyloidogenic intermediates: relevance for Alzheimer’s disease therapy. Acta Neurol. Scand. Suppl. 176 90–95 Occurrence Handle10.1034/j.1600-0404.2000.00313.x Occurrence Handle1:STN:280:DC%2BD3M7lvFWisQ%3D%3D Occurrence Handle11261811

    Article  CAS  PubMed  Google Scholar 

  53. C. Soto (1999a) ArticleTitlePlaque busters: strategies to inhibit amyloid formation in Alzheimer’s disease. Mol Med Today. 5 343–350 Occurrence Handle1:CAS:528:DyaK1MXlslehurY%3D

    CAS  Google Scholar 

  54. C. Soto (1999b) ArticleTitleAlzheimer’s and prion disease as disorders of protein conformation: implications for the design of novel therapeutic approaches. J. Mol. Med. 77 412–418 Occurrence Handle1:CAS:528:DyaK1MXkvV2rt7w%3D

    CAS  Google Scholar 

  55. C. Soto (2001) ArticleTitleProtein misfolding and disease; protein refolding and therapy. FEBS Lett. 498 204–207 Occurrence Handle10.1016/S0014-5793(01)02486-3 Occurrence Handle1:CAS:528:DC%2BD3MXksVGksr4%3D Occurrence Handle11412858

    Article  CAS  PubMed  Google Scholar 

  56. E. Terzi G. Holzemann J. Seelig (1995) ArticleTitleSelf-association of beta-amyloid peptide (1–40) in solution and binding to lipid membranes. J. Mol Biol. 252 633–642 Occurrence Handle10.1006/jmbi.1995.0525 Occurrence Handle1:CAS:528:DyaK2MXos1OhtL0%3D Occurrence Handle7563079

    Article  CAS  PubMed  Google Scholar 

  57. L.O. Tjernberg J. Näslund F. Lindqvist J. Johansson A.R. Karlström J. Thyberg L. Terenius C. Nordstedt (1996) ArticleTitleArrest of β-amyloid fibril formation by a pentapeptide ligand. J. Biol. Chem. 271 8545–8548 Occurrence Handle10.1074/jbc.271.15.8545 Occurrence Handle1:CAS:528:DyaK28Xitlegu7k%3D Occurrence Handle8621479

    Article  CAS  PubMed  Google Scholar 

  58. J. Vargas J.M. Alarcon E. Rojas (2000) ArticleTitleDisplacement currents associated with the insertion of Alzheimer disease amyloid β-peptide into planar bilayer membranes. Biophys J. 79 934–944 Occurrence Handle1:CAS:528:DC%2BD3cXlsFOgurk%3D Occurrence Handle10920024

    CAS  PubMed  Google Scholar 

  59. S.J. Wood L. MacKenzie B. Maleeff M.R. Hurle R. Wetzel (1996) ArticleTitleSelective inhibition of Abeta fibril formation. J. Biol Chem. 271 4086–4092 Occurrence Handle10.1074/jbc.271.48.30392 Occurrence Handle1:CAS:528:DyaK28XhtlSmsL0%3D Occurrence Handle8626745

    Article  CAS  PubMed  Google Scholar 

  60. S.J. Wood R. Wetzel J.D. Martin M.R. Hurle (1995) ArticleTitleProlines and amyloidogenicity in fragments of the Alzheimer’s peptide beta/A4. Biochemistry. 34 724–730 Occurrence Handle1:CAS:528:DyaK2MXjtVyrtbw%3D Occurrence Handle7827029

    CAS  PubMed  Google Scholar 

  61. B.L. Yankner L.K. Duffy D.A. Kirschner (1990a) ArticleTitleNeurotropic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 250 279–282 Occurrence Handle1:CAS:528:DyaK3MXlslansg%3D%3D

    CAS  Google Scholar 

  62. Y.J. Zhu H. Lin R. Lal (2000) ArticleTitleFresh and nonfibrillar amyloid β protein(l–40) induces rapid cellular degeneration in aged human fibroblasts evidence for AβP-channel-mediated cellular toxicity. FASEB J. 14 1244–1254 Occurrence Handle1:CAS:528:DC%2BD3cXjvFyjtL4%3D Occurrence Handle10834946

    CAS  PubMed  Google Scholar 

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Acknowledgements

The author thanks Dr. H.B. Pollard and Dr. D. Mears for invaluable comments and discussion, and Mr. M. Doh for technical assistance. This work was supported by a grant from The Alzheimer’s Association of America.

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  1. Department of Anatomy, Physiology and Genetics, and Institute for Molecular Medicine, Uniformed Services, University School of Medicine, USUHS, Bethesda, MD, 20814, USA

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Arispe, N. Architecture of the Alzheimer’s AβP Ion Channel Pore . J. Membrane Biol. 197, 33–48 (2004). https://doi.org/10.1007/s00232-003-0638-7

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