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The Journal of Membrane Biology

, Volume 202, Issue 1, pp 1–10 | Cite as

Amyloid Peptide Channels

Topical Review

Abstract

At least 16 distinct clinical syndromes including Alzheimer’s disease (AD), Parkinson’s disease (PD), rheumatoid arthritis, type II diabetes mellitus (DM), and spongiform encephelopathies (prion diseases), are characterized by the deposition of amorphous, Congo red-staining deposits known as amyloid. These “misfolded” proteins adopt β-sheet structures and aggregate spontaneously into similar extended fibrils despite their widely divergent primary sequences. Many, if not all, of these peptides are capable of forming ion-permeable channels in vitro and possibly in vivo. Common channel properties include irreversible, spontaneous insertion into membranes, relatively large, heterogeneous single-channel conductances, inhibition of channel formation by Congo red, and blockade of inserted channels by Zn2+. Physiologic effects of amyloid, including Ca2+ dysregulation, membrane depolarization, mitochondrial dysfunction, inhibition of long-term potentiation (LTP), and cytotoxicity, suggest that channel formation in plasma and intracellular membranes may play a key role in the pathophysiology of the amyloidoses.

Keywords

Alzheimer’s Amyloid deposits Prion Pores Lipid bilayers Aβ channels 

Notes

Acknowledgements

Part of this work was supported by grants from the Alzheimer’s Association, NINCDS, and NIMH

References

  1. Anguiano, M., Nowak, R.J., Lansbury, P.T.,Jr 2002Protofibrillar islet amyloid polypeptide permeabilizes synthetic vesicles by a pore-like mechanism that may be relevant to type II diabetesBiochemistry411133811343CrossRefPubMedGoogle Scholar
  2. Arispe, N., Rojas, E., Pollard, H.B. 1993aAlzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminumProc. Natl. Acad. Sci. USA90567571Google Scholar
  3. Arispe, N., Pollard, H.B., Rojas, E. 1993bGiant multilevel cation channels formed by Alzheimer disease amyloid beta-protein [A beta P-(1–40)] in bilayer membranesProc. Natl. Acad. Sci. USA901057310577Google Scholar
  4. Arispe, N. 2004Characterization of the Alzheimer’s AβP channel poreJ. Membrane Biol.1973348CrossRefGoogle Scholar
  5. Arispe, N., Doh, M. 2002Plasma membrane cholesterol controls the cytotoxicity of Alzheimer’s disease AβP (1–40) and (1–42) peptidesFASEB J.615261536CrossRefGoogle Scholar
  6. Arispe, N., Pollard, H.B., Rojas, E. 1996Zn2+ interaction with Alzheimer amyloid beta protein calcium channelsProc. Natl. Acad. Sci. USA9317101715CrossRefPubMedGoogle Scholar
  7. Azimova, R.K., Kagan, B.L. 2003Ion channels formed by a fragment of alpha-synuclein (NAC) in lipd membranesBiophys. J.8453aGoogle Scholar
  8. Bahadi, R., Farrelly, P.V., Kenna, B.L., Kourie, J.I., Tagliayini, F., Forloni, G.,  et al. 2003bChannels formed with a mutant prion protein Prp (82–146) homologous to a 7-kDa fragment in diseased brain of GSS patientsAm. J. Physiol. Cell Physiol.285C862C872Google Scholar
  9. Baptista, M.J., Cookson, M.R., Miller, D.W. 2004Parkin and alpha-synuclein: opponent actions in the pathogenesis of Parkinson’s diseaseNeuroscientist106372CrossRefPubMedGoogle Scholar
  10. Berkowitz, B.A., Bevins, C.L., Zasloff, M.A. 1990Magainins: a new family of membrane-active host defense peptidesBiochem. Pharmacol.39625629CrossRefPubMedGoogle Scholar
  11. Brinckerhoff, C.E., Mitchell, T.I., Karmilowicz, M.J., Kluve-Beckerman, B., Benson, M.D. 1989Autocrine induction of collagenase by serum amyloid A-like and beta 2-microglobulin-like proteins [see comments]Science243655657PubMedGoogle Scholar
  12. Caughey, B., Lansbury, P.T.,Jr 2003Protofibrils, Pores, Fibrils, and Neurodegeneration: Separating the Responsible Protein Aggregates from the Innocent BystandersAnnu. Rev. Neurosci.26267298CrossRefPubMedGoogle Scholar
  13. Chen, Q.S., Kagan, B.L., Hirakura, Y., Xie, C.W. 2000Impairment of hippocampal long-term potentiation by Alzheimer amyloid beta-peptidesJ. Neurosci. Res.606572CrossRefPubMedGoogle Scholar
  14. Gioia, L., Selvaggini, C., Ghibaudi, E.,  et al. 1994Conformational polymorphism of the amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion proteinJ. Biol. Chem.26978597862PubMedGoogle Scholar
  15. Drueke, T.B. 1998Dialysis-related amyloidosisNephrol. Dial. Transplant.135864CrossRefPubMedGoogle Scholar
  16. Durell, S.R., Guy, H.R., Arispe, N., Rojas, E., Pollard, H.B. 1994Theoretical models of the ion channel structure of amyloid beta-proteinBiophys. J.6721372145PubMedGoogle Scholar
  17. Falk, R.H., Comenzo, R.L., Skinner, M. 1997The systemic amyloidosesN. Engl. J. Med.337898909CrossRefPubMedGoogle Scholar
  18. Farrelly, P.V., Kenna, B.L., Laohachai, K.L., Bahadi, R., Salmona, M., Forloni, G., Kourie, J.L.,  et al. 2003Quinacrine blocks PrP (106–126)-formed channelsJ. Neurosci. Res.74934941CrossRefPubMedGoogle Scholar
  19. Forloni, G., Chiesa, R., Smiroldo, S., Verga, L., Salmona, M., Tagliavini, F.,  et al. 1993Apoptosis-mediated neurotoxicity induced by chronic application of beta amyloid fragment 25–35Neuroreport4523526PubMedGoogle Scholar
  20. Fraser, S.P., Suh, Y.H., Djamgoz, M.B. 1997Ionic effects of the Alzheimer’s disease beta-amyloid precursor protein and its metabolic fragmentsTrends Neurosci.206772CrossRefPubMedGoogle Scholar
  21. Furukawa, K., Abe, Y., Akaike, N. 1994Amyloid beta protein-induced irreversible current in rat cortical neuronesNeuroreport520162018PubMedGoogle Scholar
  22. Gasset, M., Baldwin, M.A., Lloyd, D.H., Gabriel, J.M., Holtzman, D.M., Cohen, F., Fletterick, R., Prusiner, S.B. 1992Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloidProc. Natl. Acad. Sci. USA891094010944PubMedGoogle Scholar
  23. Harper, J.D., Lansbury, P.T.,Jr 1997Models of amyloid seeding in Alzheimer’s disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteinsAnnu. Rev. Biochem.66385407CrossRefPubMedGoogle Scholar
  24. Hegde, R.S., Mastrianni, J.A., Scott, M.R.,  et al. 1998A transmembrane form of the prion protein in neurodegenerative diseaseScience279827834CrossRefPubMedGoogle Scholar
  25. Hirakura, Y., Kagan, B.L. 2001Pore formation by beta-2-microglobulin: a mechanism for the pathogenesis of dialysis-associated amyloidosisAmyloid894100PubMedGoogle Scholar
  26. Hirakura, Y., Lin, M.C., Kagan, B.L. 1999Alzheimer amyloid abeta1–42 channels: effects of solvent, pH, and Congo RedJ. Neurosci. Res.57458466CrossRefPubMedGoogle Scholar
  27. Hirakura, Y., Azimov, R., Azimova, R., Kagan, B.L. 2000Polyglutamine-induced ion channels: A possible mechanism for the neurotoxicity of huntington and other CAG repeat diseasesJ. Neurosci. Res.60490494CrossRefPubMedGoogle Scholar
  28. Hirakura, Y., Azimova, R., Azimov, R., Kagan, B.L. 2001Ion channels with different selectivity formed by transthyretinBiophys. J.80120aGoogle Scholar
  29. Hirakura, Y., Carreras, I., Sipe, J.D., Kagan, B.L. 2002Channel formation by serum amyloid A: a potential mechanism for amyloid pathogenesis and host defenseAmyloid91323PubMedGoogle Scholar
  30. Janson, J., Ashley, R.H., Harrison, D., McIntyre, S., Butler, P.C. 1999The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particlesDiabetes48491498PubMedGoogle Scholar
  31. Kagan, B.L. 1983Mode of action of yeast killer toxins: channel formation in lipid bilayer membranesNature302709711CrossRefPubMedGoogle Scholar
  32. Kagan, B.L., Finkelstein, A., Colombini, M. 1981Diphtheria toxin fragments forms large pores in phospholipid bilayer membranesProc. Natl. Acad. Sci. USA7849504954PubMedGoogle Scholar
  33. Kagan, B.L., Selsted, M.E., Ganz, T., Lehrer, R.I. 1990ProcNat. Acad. Sci. USA87210214Google Scholar
  34. Kawahara, M., Arispe, N., Kuroda, Y., Rojas, E. 1997Alzheimer’s disease amyloid beta-protein forms Zn2+-sensitive, cation-selective channels across excised membrane patches from hypothalamic neuronsBiophys. J.736775PubMedGoogle Scholar
  35. Kawahara, M., Kuroda, Y., Arispe, N., & Rojas, E. 2000Alzheimer’s beta-amyloid, human islet amylin, and prion protein fragment evoke intracellular free calcium elevations by a common mechanism in a hypothalamic GnRH neuronal cell lineJ. Biol. Chem.2751407714083CrossRefPubMedGoogle Scholar
  36. Kim, H.S., Lee, J.H., Lee, J.P.,  et al. 2002Amyloid beta peptide induces cytochrome C release from isolated mitochondriaNeuroreport1319891993CrossRefPubMedGoogle Scholar
  37. Kourie, J.I. 1999Characterization of a C-type natriuretic peptide (CNP-39)-formed cation-selective channel from platypus (Omithorhynchus anatinus) venomJ. Physiol.518359369CrossRefPubMedGoogle Scholar
  38. Kourie, J.I., Culverson, A. 2000Prion peptide fragment PrP[106–126] forms distinct cation channel typesJ. Neurosci. Res.62120133CrossRefPubMedGoogle Scholar
  39. Kourie, J.I., Culverson, A.L., Farrelly, P.V., Henry, C.L., Laohachai, K.N. 2002Heterogeneous amyloid-formed ion channels as a common cytotoxic mechanism: implications for therapeutic strategies against amyloidosisCell Biochem. Biophys.36191207CrossRefPubMedGoogle Scholar
  40. Kourie, J.I., Kenna, B.L., Tew, D., Jobling, M.F., Curtain, C.C., Masters, C.L. 2003Copper modulation of ion channels of PrP[106–126] mutant prion peptide fragmentsJ. Membrane Biol.1933545CrossRefGoogle Scholar
  41. Kourie, J.I., Hanna, E.A., Henry, C.L. 2001aProperties and modulation of alpha human atrial natriuretic peptide (alpha-hANP)-formed ion channelsCan J. Physiol Pharmacol79654664CrossRefGoogle Scholar
  42. Kourie, J.I., Henry, C.L., Farrelly, P. 2001bDiversity of amyloid beta protein fragment [1–40]-formed channelsCell Mol Neurobiol21255284CrossRefGoogle Scholar
  43. Lashuel, H.A., Hartley, D.M., Petre, B.M., Wall, J.S., Simon, M.N., Walz, T.,  et al. 2003Mixtures of wild-type and a pathogenic (E22G) form of Abeta40 in vitro accumulate protofibrils, including amyloid poresJ. Mol. Biol.332795808CrossRefPubMedGoogle Scholar
  44. Lashuel, H.A., Petre, B.M., Wall, J., Simon, M., Nowak, R.J., Walz, T.,  et al. 2002Alpha-synuclein, especially the Parkinson’s disease-associated mutants, forms pore-like annular and tubular protofibrilsJ. Mol. Biol.32210891102CrossRefPubMedGoogle Scholar
  45. Li, S.H., Li, X.J. 2004Huntingtin-protein interactions and the patho-genesis of Huntington’s diseaseTrends Genet20146154CrossRefPubMedGoogle Scholar
  46. Lin, M.C. 1996. Channel formation by amyloldogenic neurotoxic and neurodegenerative disease related peptides. Ph.D. dissertation, Division of Neuroscience, UCLAGoogle Scholar
  47. Lin, M.C., Kagan, B.L. 2002Electrophysiologic properties of channels induced by Abeta25–35 in planar lipid bilayersPeptides2312151228CrossRefPubMedGoogle Scholar
  48. Lin, M.C., Mirzabekov, T., Kagan, B.L. 1997Channel formation by a neurotoxic prion protein fragmentJ. Biol. Chem.2724447CrossRefPubMedGoogle Scholar
  49. Lin, H., Zhu, Y.J., Lal, R. 1999Amyloid beta protein (1–40) forms calcium-permeable, Zn2+ sensitive channel in reconstituted lipid vesiclesBiochemistry381118911196CrossRefPubMedGoogle Scholar
  50. Liu, C.C., Persechini, P.M., Young, J.D. 1995Perforin and lymphocyte-mediated cytolysisImmunol. Rev146145175PubMedGoogle Scholar
  51. Lorenzo, A., Razzaboni, B., Weir, G.C., Yankner, B.A. 1994Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitusNature368756760CrossRefPubMedGoogle Scholar
  52. Malisauskas, M., Zamotin, V., Jass, J., Noppe, W., Dobson, C.M., Morozova-Roche, L.A. 2003Amyloid protofilaments from the calcium-binding protein equine lysozyme: formation of ring and linear structures depends on pH and metal ion concentrationJ. Mol. Biol.330879890CrossRefPubMedGoogle Scholar
  53. Manunta, M., Kunz, B., Sandmeier, E., Christen, P., Schindler, H. 2000Reported channel formation by prion protein fragment 106–126 in planar lipid bilayers cannot be reproduced [letter]FEBS Lett.474255256CrossRefPubMedGoogle Scholar
  54. McCarthy, R.E.,3rd, Kasper, E.K. 1998A review of the amyloidoses that infiltrate the heartClin Cardiol21547552PubMedGoogle Scholar
  55. McKeith, I., Mintzer, J., Aarsland, D., Burn, D., Chiu, H., Cohen-Mansfield, J.,  et al. 2004Dementia with Lewy bodiesLancet Neurol.31928CrossRefPubMedGoogle Scholar
  56. McLean, L.R., Balasubramaniam, A. 1992Promotion of beta-structure by interaction of diabetes-associated polypeptide (amylin) with phosphatidylcholineBiochim. Biophys. Acta1122317320PubMedGoogle Scholar
  57. Merlini, G., Bellotti, V. 2003Molecular mechanisms of amyloidosisN. Engl. J. Med.349583596CrossRefPubMedGoogle Scholar
  58. Mirzabekov, T.A., Lin, M.C., Kagan, B.L. 1996Pore formation by the cytotoxic islet amyloid peptide amylinJ. Biol. Chem.27119881992CrossRefPubMedGoogle Scholar
  59. Mirzabekov, T., Lin, M.C., Yuan, W.L., Marshall, P.J., Carman, M., Tomaselli, K., Lieberburg, I., Kagan, B.L. 1994Channel formation in planar lipid bilayers by a neurotoxic fragment of the beta-amyloid peptideBiochem. Biophys. Res. Commun.20211421148CrossRefPubMedGoogle Scholar
  60. Moe, S.M., Sprague, S.M. 1992Beta 2-microglobulin induces calcium efflux from cultured neonatal mouse calvariaeAm. J. Physiol.263F540F545PubMedGoogle Scholar
  61. Monoi, H., Futaki, S., Kugimiya, S., Minakata, H., Yoshihara, K. 2000Poly-L-glutamine forms cation channels: relevance to the pathogenesis of the polyglutamine diseases [see comments]Biophys. J.7828922899PubMedGoogle Scholar
  62. Pan, K.M., Bladwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D.,  et al. 1993Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteinsProc. Natl. Acad. Sci. USA901096210966PubMedGoogle Scholar
  63. Panov, A.V., Gutekunst, C.A., Leavitt, B.R., Hayden, M.R., Burke, J.R., Strittmatter, W.J.,  et al. 2002Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutaminesNat. Neurosci.5731736PubMedGoogle Scholar
  64. Petersen, J., Kang, M.S. 1994In vivo effect of beta 2-microglobulin on bone resorptionAm. J. Kidney Dis.23726730PubMedGoogle Scholar
  65. Petosa, C., Collier, R.J., Klimpel, K.R., Leppla, S.H., Liddington, R.C. 1997Crystal structure of the anthrax toxin protective antigenNature385833838CrossRefPubMedGoogle Scholar
  66. Pike, C.J., Burdick, D., Walencewicz, A.J., Glabe, C.G., Cotman, C.W. 1993Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly stateJ. Neurosci.1316761687PubMedGoogle Scholar
  67. Qi, J.S., Qiao, J.T. 2001Amyloid beta-protein fragment 31–35 forms ion channels in membrane patches excised from rat hippocampal neuronsNeuroscience105845852CrossRefPubMedGoogle Scholar
  68. Rhee, S.K., Quist, A.P., Lal, R. 1998Amyloid beta protein-(1–42) forms calcium-permeable, Zn2+-sensitive channelJ. Biol. Chem.2731337913382CrossRefPubMedGoogle Scholar
  69. Sanderson, K.L., Butler, L., Ingram, V.M. 1997Aggregates of a beta-amyloid peptide are required to induce calcium currents in neuron-like human teratocarcinoma cells: relation to Alzheimer’s diseaseBrain Res.744714CrossRefPubMedGoogle Scholar
  70. Schein, S.J., Kagan, B.L., Finkelstein, A. 1978Colicin K acts by forming voltage-dependent channels in phospholipid bilayer membranesNature276159163PubMedGoogle Scholar
  71. Selkoe, D.J. 2002Alzheimer’s disease is a synaptic failureScience298789791CrossRefPubMedGoogle Scholar
  72. Selkoe, D.J. 2003Folding proteins in fatal waysNature426900904CrossRefPubMedGoogle Scholar
  73. Sipe, J.D. 2000Serum amyloid A: from fibril to functionCurrent status. Amyloid71012Google Scholar
  74. Sipe, J.D., Cohen, A.S. 2000Review: history of the amyloid fibrilJ. Struct. Biol.1308898CrossRefPubMedGoogle Scholar
  75. Sokolov, Y., Mirzabekov, T., Martin, D.W., Lehrer, R.I., Kagan, B.L. 1999Membrane channel formation by antimicrobial protegrinsBiochim. Biophys. Acta14202329PubMedGoogle Scholar
  76. Song, L., Hobaugh, M.R., Shustak, C., Cheley, S., Bayley, H., Gouaux, J.E. 1996Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane poreScience27418591866CrossRefPubMedGoogle Scholar
  77. Stipani, V., Galluci, E., Micelli, S., Picciarelli, V., Benz, R. 2001Channel formation by salmon and human calcitonin in black lipid membranesBiophys. J.8133323338PubMedGoogle Scholar
  78. Volles, M.J., Lansbury, P.T.,Jr 2002Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson’s disease-linked mutations and occurs by a pore-like mechanismBiochemistry4145954602CrossRefPubMedGoogle Scholar
  79. Walsh, D.M., Klyubin, I., Fadeeva, J.V., Cullen, W.K., Anwyl, R., Wolfe, M.S.,  et al. 2002Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivoNature416535539CrossRefPubMedGoogle Scholar
  80. Wang, Z.L., Bennet, W.M., Ghatei, M.A., Byfield, P.G., Smith, D.M., Bloom, S.R. 1993Influence of islet amyloid polypeptide and the 8–37 fragment of islet amyloid polypeptide on insulin release from perifused rat isletsDiabetes42330335PubMedGoogle Scholar
  81. Wang, L., Lashuel, H.A., Walz, T., Colon, W. 2002Murine apolipoprotein serum amyloid A in solution forms a hexamer containing a central channelProc. Natl. Acad. Sci. USA991594715952CrossRefPubMedGoogle Scholar
  82. Westermark, P., Wilander, E. 1978The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitusDiabetologia15417421CrossRefPubMedGoogle Scholar
  83. Weiss, J.H., Pike, C.J., Cotman, C.W. 1994Ca2+ channel blockers attenuate beta-amyloid peptide toxicity to cortical neurons in cultureJ. Neurochem.62372375PubMedGoogle Scholar
  84. Zhu, Y.J., Lin, H., Lal, R. 2000Fresh and nonfibrillar amyloid beta protein (1–40) induces rapid cellular degeneration in aged human fibroblasts: evidence for AbetaP-channel-mediated cellular toxicityFASEB J.1412441254PubMedGoogle Scholar

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© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of Psychiatry, Neuropsychiatric Institute, David Geffen School of MedicineUCLALos AngelesUSA

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