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. 2001 Jun;21(3):173–213. doi: 10.1023/A:1010932603406

Mechanisms of Amyloid β Protein-Induced Modification in Ion Transport Systems: Implications for Neurodegenerative Diseases

Joseph I Kourie 1
PMCID: PMC11533863  PMID: 11569534

Abstract

1. Alzheimer's disease (AD) is a neurodegenerative disorder that affects the cognitive function of the brain. Pathological changes in AD are characterized by the formation of amyloid plaques and neurofibrillary tangles as well as extensive neuronal loss. Abnormal proteolytic processing of amyloid precursor protein (APP) is the central step that leads to formation of amyloid plaque, neurofibrillary tangles, and neuronal loss.

2. The plaques, which accumulate extracellularly in the brain, are composed of aggregates and cause direct neurotoxic effects and/or increase neuronal vulnerability to excitotoxic insults. The aggregates consist of soluble pathologic amyloid beta peptides AβP[1–42] and AβP[1–43] and soluble nonpathologic AβP[1–40]. Both APP and AβP interact with ion transport systems. AβP induces a wide range of effects as the result of activating a cascade of mechanisms.

3. The major mechanisms proposed for AβP-induced cytotoxicity involve the loss of Ca2+ homeostasis and the generation of reactive oxygen species (ROS). The changes in Ca2+ homeostasis could be the result of (1) changes in endogenous ion transport systems, e.g. Ca2+ and K+ channels and Na+/K+-ATPase, and membrane receptor proteins, such as ligand-driven ion channels and G-protein-driven releases of second messengers, and (2) formation of heterogeneous ion channels.

4. The consequences of changes in Ca2+-homeostasis-induced generation of ROS are (a) direct modification of intrinsic ion transport systems and their regulatory mechanisms, and (b) indirect effects on ion transport systems via peroxidation of phospholipids in the membrane, inhibition of phosphorylation, and reduction of ATP levels and cytoplasmic pH.

5. We propose that in AD, AβP with its different conformations alters cell regulation by modifying several ion transport systems and also by forming heterogeneous ion channels. The changes in membrane transport systems are proposed as early steps in impairing neuronal function preceding plaque formation. We conclude that these changes damage the membrane by compromising its integrity and increasing its ion permeability. This mechanism of membrane damage is not only central for AD but also may explain other malfunctioned protein-processing–related pathologies.

Keywords: ion channel diseases, protein aggregation, neurodegeneration, beta amyloid, membrane physiology, Alzheimer's disease, neurofibrillary tangles, senile plaques

REFERENCES

  1. Alkon, D. L., Amaral, D. G., Bear, M. F., Black, J., Carew, T. J., Cohen, N. J., Disterhoft, J. F., Eichenbaum, H., Golski, S., Gorman, L. K., Lynch, G., McNaughton, B. L., Mishkin, N., Moyer, J. R., Olds, J. L., Olton, D. S., Otto, T., Squire, L. R., Staubli, U., Thompson, L. T., and Wible, C. (1991). Learning and memory. Brain Res. Brain Res. Rev.16:193-220. [DOI] [PubMed] [Google Scholar]
  2. Arispe, N., Pollard, H. B., and Rojas, E. (1993a). Giant multilevel cation channels formed by Alzheimer disease amyloid beta-protein [AβP-(1–40)] in bilayer membranes. Proc. Natl. Acad. Sci. USA90:10573-10577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arispe, N., Pollard, H. B., and Rojas, E. (1994). Beta-amyloid Ca2+-channel hypothesis for neuronal death in Alzheimer disease. Mol. Cell. Biochem.140:119-125. [DOI] [PubMed] [Google Scholar]
  4. Arisped, N., Pollard, H. B., and Rojas, E. (1996). Zn2+ interaction with Alzheimer amyloid beta protein calcium channels. Proc. Natl. Acad. Sci. USA93:1710-1715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arispe, N., Rojas, E., and Pollard, H. B. (1993b). Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: Blockade by tromethamine and aluminum. Proc. Natl. Acad. Sci. USA90:567-571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barger, S. W., and Mattson, M. P. (1995). The secreted form of the Alzheimer's β-amyloid precursor protein stimulates a membrane-associated guanylate cyclase. Biochem. J.311:45-47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Barrow, C. J., Yasuda, A., Kenny, P. T., and Zagorski, M. G. (1992). Solution conformations and aggregational properties of synthetic amyloid beta-peptides of Alzheimer's disease. Analysis of circular dichroism spectra. J. Mol. Biol.225:1075-1093. [DOI] [PubMed] [Google Scholar]
  8. Barrow, C. J., and Zagorski, M. G. (1991). Solution structures of beta peptide and its constituent fragments: relation to amyloid deposition. Science253:179-182. [DOI] [PubMed] [Google Scholar]
  9. Behl, C., Davis, J., Cole, G. M., and Schubert, D. (1992). Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem. Biophys. Res. Commun.186:944-950. [DOI] [PubMed] [Google Scholar]
  10. Behl, C., Davis, J. B., Lesley, R., and Schubert, D. (1994). Hydrogen peroxide mediates amyloid β protein toxicity. Cell77:817-827. [DOI] [PubMed] [Google Scholar]
  11. Blanc, E. M., Toborek, M., Mark, R. J., Hennig, B., and Mattson, M. P. (1997). Amyloid beta-peptide induces cell monolayer albumin permeability, impairs glucose transport, and induces apoptosis in vascular endothelial cells. J. Neurochem.68:1870-1881. [DOI] [PubMed] [Google Scholar]
  12. Boddeke, H. W., Meigel, I., Swoboda, R., and Boeijinga, P. H. (1994). The amyloid precursor protein fragment His 657-Lys 676 inhibits noradrenaline-and enkephaline-induced suppression of voltage sensitive calcium currents in NG108-15 hybrid cells. Neuroscience62:631-634. [DOI] [PubMed] [Google Scholar]
  13. Bores, G. M., Smith, C. P., Wirtz-Brugger, F., and Giovanni, A. (1998). Amyloid beta-peptides inhibit Na+/K+-ATPase: Tissue slices versus primary cultures. Brain Res. Bull.46:423-427. [DOI] [PubMed] [Google Scholar]
  14. Bourdillon, P. D., and Wilson, P. A. P. (1981). Effects of ischemia and reperfusion on calcium exchange and mechanical function in isolated rabbit myocardium. Cardiovasc Res.15:121-130. [DOI] [PubMed] [Google Scholar]
  15. Brera, B., Serrano, A., and De Ceballos, M. L. (2000). Beta-amyloid peptides are cytotoxic to astrocytes in culture: A role for oxidative stress. Neurobiol. Dis.7:395-405. [DOI] [PubMed] [Google Scholar]
  16. Brorson, J. R., Bindokas, V. P., Iwama, T., Marcuccilli, C. J., Chisholm, J. C., and Miller, R. J. (1995). The Ca2+ influx induced by beta-amyloid peptide 25–35 in cultured hippocampal neurons results from network excitation. J. Neurobiol.26:325-338. [DOI] [PubMed] [Google Scholar]
  17. Bush, A. I., Pettingell, W. H., Jr., Paradis, M. D., and Tanzi, R. E. (1994). Modulation of A beta adhesiveness and secretase site cleavage by zinc. J. Biol. Chem.269:12152-1258. [PubMed] [Google Scholar]
  18. Buxbaum, J. D., Ruefli, A. A., Parker, C. A., Cypess, A. M., and Greengard, P. (1994). Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner. Proc. Natl. Acad. Sci. USA91:4489-4493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Carette, B., Poulain, P., and Delacourte, A. (1993). Electrophysiological effects of 25–35 amyloid-beta-protein on guinea-pig lateral septal neurons. Neurosci. Lett.151:111-114. [DOI] [PubMed] [Google Scholar]
  20. Castle, A. L., Kuo, C. H., Han, D. H., and Ivy, J. L. (1998). Amylin-mediated inhibition of insulin-stimulated glucose transport in skeletal muscle. Am. J. Physiol.275:E531-E536. [DOI] [PubMed] [Google Scholar]
  21. Chalmoniuk, M., and Strosznajder, J. B. (1999). Aging modulates nitric oxide synthesis and cGMP levels in hippocampus and cerebellum. Effects of amyloid beta peptide. Mol. Chem. Neuropathol.35:77-95. [DOI] [PubMed] [Google Scholar]
  22. Chan, S. L., and Mattson, M. P. (1999). Caspase and calpain substrates: Roles in synaptic plasticity and cell death. J. Neurosci. Res.58:167-190. [PubMed] [Google Scholar]
  23. Chauhan, N. B., Lee, J. M., and Siegel, G. J. (1997). Na/K-ATPase mRNA levels and plaque load in Alzheimer's disease. J. Mol. Neurosci.9:151-166. [DOI] [PubMed] [Google Scholar]
  24. Chen, Q. S., Kagan, B. L., Hirakura, Y., and Xie, C. W. (2000). Impairment of hippocampal long-term potentiation by Alzheimer amyloid beta-peptides. J. Neurosci. Res.60:65-72. [DOI] [PubMed] [Google Scholar]
  25. Chi, X., Sutton, E. T., Thomas, T., and Price, J. M. (1999). The protective effect of K+ channel openers on beta-amyloid induced cerebrovascular endothelial dysfunction. Neurol. Res.21:345-351. [DOI] [PubMed] [Google Scholar]
  26. Christen, Y. (2000). Oxidative stress and Alzheimer disease. Am. J. Clin. Nutr.71:621S-629S. [DOI] [PubMed] [Google Scholar]
  27. Coetzee, W. A., Ichikawa, H., and Hearse, D. J. (1994). Oxidant stress inhibits Na+ Ca2+-exchange current in cardiac myocytes: mediation by sulfhydryl groups? Am. J. Physiol.266:H909-919. [DOI] [PubMed] [Google Scholar]
  28. Cohen, C. D., Vollmayr, B., and Aldenhoff, J. B. (1996). K+ currents of human T-lymphocytes are unaffected by Alzheimer's disease and amyloid beta protein. Neurosci. Lett.202:177-180. [DOI] [PubMed] [Google Scholar]
  29. Colom, L. V., Diaz, M. E., Beers, D. R., Neely, A., Xie, W. J., and Appel, S. H. (1998). Role of potassium channels in amyloid-induced cell death. Neurochemistry70:1925-1934. [DOI] [PubMed] [Google Scholar]
  30. Condrescu, M., Chernaya, G., Kalaria, V., and Reeves, J. P. (1997). Barium influx mediated by the cardiac sodium exchanger in transfected Chinese hamster ovary cells. J. Gen. Physiol.109:41-51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Coyle, J. T., and Puttfarcken, P. (1993). Oxidative stress, glutamate, and neurodegenerative disorders. Science262:689-695. [DOI] [PubMed] [Google Scholar]
  32. Davidson, R. M., Shajenko, L., and Donta, T. S. (1994). Amyloid beta-peptide (AβP) potentiates a nimodipine-sensitive L-type barium conductance in N1E-115 neuroblastoma cells. Brain Res.643:324-327. [DOI] [PubMed] [Google Scholar]
  33. Durell, S. R., Guy, H. R., Arispe, N., Rojas, E., and Pollard, H. B. (1994). Theoretical models of the ion channel structure of amyloid beta-protein. Biophys. J.67:137-145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ekinci, F. J., Linsley, M. D., and Shea, T. B. (2000). Beta-amyloid-induced calcium influx induces apoptosis in culture by oxidative stress rather than tau phosphorylation. Brain Res. Mol. Brain Res.76:389-395. [DOI] [PubMed] [Google Scholar]
  35. Ekinci, F. J., Malik, K. U., and Shea, T. B. (1999). Activation of the L voltage-sensitive calcium channel by mitogen-activated protein (MAP) kinase following exposure of neuronal cells to beta-amyloid. MAP kinase mediates beta-amyloid-induced neurodegeneration. J. Biol. Chem.274:30322-30327. [DOI] [PubMed] [Google Scholar]
  36. Etcheberrigaray, E., Gibson, G. E., and Alkon, D. L. (1994a). Molecular mechanisms of memory and the pathophysiology of Alzheimer's disease. Ann. NY Acad. Sci.747:245-255. [DOI] [PubMed] [Google Scholar]
  37. Etcheberrigaray, R., Ito, E., Kim, C. S., and Alkon, D. L. (1994b). Soluble beta-amyloid induction of Alzheimer's phenotype for human fibroblast K+ channels. Science264:276-279. [DOI] [PubMed] [Google Scholar]
  38. Fiori, M. G., Salvi, F., Plasmati, R., Tessari, F., Bianchi, R., and Tassinari, C. A. (1994). Amyloid deposits inside myocardial fibers in transthyretin-Met30 familial amyloidotic polyneuropathy. A histological and biochemical study. Cardiology85:145-153. [DOI] [PubMed] [Google Scholar]
  39. Fraser, P. E., Nguyen, J. T., Chin, D. T., and Kirschner, D. A. (1992). Effects of sulfate ions on Alzheimer beta/A4 peptide assemblies: Implications for amyloid fibril-proteoglycan interactions. J. Neurochem.59:1531-1540. [DOI] [PubMed] [Google Scholar]
  40. Fraser, S. P., Suh, Y. H., Chong, Y. H., and Djamgoz, M. B. (1996). Membrane currents induced in Xenopus oocytes by the C-terminal fragment of the beta-amyloid precursor protein. J. Neurochem.66:2034-2040. [DOI] [PubMed] [Google Scholar]
  41. Furukawa, K., Abe, Y., and Akaike, N. (1994). Amyloid beta protein-induced irreversible current in rat cortical neurones. Neuroreport5:2016-2018. [DOI] [PubMed] [Google Scholar]
  42. Furukawa, K., Barger, S. W., Blalock, E. M., and Mattson, M. P. (1996). Activation of K+ channels and suppression of neuronal activity by secreted beta-amyloid-precursor protein. Nature379:74-78. [DOI] [PubMed] [Google Scholar]
  43. Gegelashvili, G., and Schousboe, A. (1997). High affinity glutamate transporters: Regulation of expression and activity. Mol. Pharmacol.52:6-15. [DOI] [PubMed] [Google Scholar]
  44. Golde, T. E., Estus, S., Younkin, L. H., Selkoe, D. J., and Younkin, S. G. (1992). Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science255:728-730. [DOI] [PubMed] [Google Scholar]
  45. Goldhaber, J. I. (1996). Free radicals enhance Na+/Ca2+ exchange in ventricular myocytes. Am. J. Physiol.271:H823-H833. [DOI] [PubMed] [Google Scholar]
  46. Good, T. A., and Murphy, R. M. (1996). Effect of beta-amyloid block of the fast-inactivating K+ channel on intracellular Ca2+ and excitability in a modeled neuron. Proc. Natl. Acad. Sci. USA93:15130-15135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Good, T. A., Smith, D. O., and Murphy, R. M. (1996). Beta-amyloid peptide blocks the fast-inactivating K+ current in rat hippocampal neurons. Biophys. J.70:296-304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Goodman, Y., and Mattson, M. P. (1996). K+ channel openers protect hippocampal neurons against oxidative injury and amyloid beta-peptide toxicity. Brain Res.706:328-332. [DOI] [PubMed] [Google Scholar]
  49. Guo, Z. H., Kindy, M. S., Kruman, I., and Mattson, M. P. (2000). ALS-linked Cu/Zn-SOD mutation impairs cerebral synaptic glucose and glutamate transport and exacerbates ischemic brain injury. J. Cereb. Blood Flow Metab.20:463-468. [DOI] [PubMed] [Google Scholar]
  50. Guo, Z. H., and Mattson, M. P. (2000). Neurotrophic factors protect cortical synaptic terminals against amyloid and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function. Cereb. Cortex10:50-57. [DOI] [PubMed] [Google Scholar]
  51. Haass, C., Koo, E. H., Mellon, A., Hung, A. Y., and Selkoe, D. J. (1992). Targeting of cell-surface beta-amyloid precursor protein to lysosomes: Alternative processing into amyloid-bearing fragments. Nature357:500-503. [DOI] [PubMed] [Google Scholar]
  52. Haass, C., and Selkoe, D. J. (1993). Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell75:1039-1042. [DOI] [PubMed] [Google Scholar]
  53. Hardy, J., and Allsop, D. (1991). Amyloid deposition as the central event in the aetiology of Alzheimer's disease. TIPS12:383-388. [DOI] [PubMed] [Google Scholar]
  54. Harris, M. E., Wang, Y., Pedigo, N. W. Jr., Hensley, K., Butterfield, D. A., and Carney, J. M. (1996). Amyloid beta peptide (25–35) inhibits Na+-dependent glutamate uptake in rat hippocampal astrocyte cultures. J. Neurochem.67:277-286. [DOI] [PubMed] [Google Scholar]
  55. Heurteaux, C., Bertaina, V., Widmann, C., and Lazdunski, M. (1993). K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid beta-protein precursor genes and neuronal death in rat hippocampus. Neurobiology90:9431-9435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Hilbich, C., Kisters-Woike, B., Reed, J., Masters, C. L., and Beyreuther, K. (1991a). Human and rodent sequence analogs of Alzheimer's amyloid beta A4 share similar properties and can be solubilized in buffers of pH 7.4. Eur. J. Biochem.201:61-69. [DOI] [PubMed] [Google Scholar]
  57. Hilbich, C., Kisters-Woike, B., Reed, J., Masters, C. L., and Beyreuther, K. (1991b). Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer's disease. J. Mol. Biol.218:149-163. [DOI] [PubMed] [Google Scholar]
  58. Hirakura, Y., and Kagan, B. L. (1999). Channel formation in the pathogenesis of Alzheimer's disease and other amyloidoses. Einstein Quart. J. Biol. Med.16:124-129. [Google Scholar]
  59. Hirakura, Y., Lin, M. C., and Kagan, B. L. (1999). Alzheimer amyloid Aβ1-42 channels: Effects of solvent, pH, and Congo Red. J. Neurosci. Res.57:458-466. [PubMed] [Google Scholar]
  60. Hirakura, Y., Satoh, Y., Hirashima, N., Suzuki, T., Kagan, B. L., and Kirino, Y. (1998). Membrane perturbation by the neurotoxic Alzheimer amyloid fragment b25–35 requires aggregation and β-sheet formation. Biochem. Mol. Biol. Int.46:787-794. [DOI] [PubMed] [Google Scholar]
  61. Hirakura, Y., Yiu, W. W., Yamamoto, A., and Kagan, B. L. (2000). Amyloid peptide channels: Blockade by zinc and inhibition by congo red. Amyloid7:194-199. [DOI] [PubMed] [Google Scholar]
  62. Hothersall, J. S., Muirhead, R. P., and Wimalawansa, S. (1990). The effect of amylin and calcitonin gene-related peptide on insulin-stimulated glucose transport in the diaphragm. Biochem. Biophys. Res. Commun.169:451-454. [DOI] [PubMed] [Google Scholar]
  63. Hu, J., and el-Fakahany, E. E. (1993a). Role of intercellular and intracellular communication by nitric oxide in coupling of muscarinic receptors to activation of guanylate cyclase in neuronal cells. J. Neurochem.61:578-585. [DOI] [PubMed] [Google Scholar]
  64. Hu, J., and el-Fakahany, E. E. (1993b). Beta-amyloid 25–35 activates nitric oxide synthase in a neuronal clone. Neuroreport4:760-762. [DOI] [PubMed] [Google Scholar]
  65. Inouye, H., Fraser, P. E., and Kirschner, D. A. (1993). Structure of beta-crystallite assemblies formed by Alzheimer beta-amyloid protein analogues: Analysis by x-ray diffraction. Biophys. J.64:502-519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Ishikawa, H., Ozawa, H., Saito, T., Takahata, N., and Takemura, H. (1998). Calcium mobilization evoked by amyloid beta-protein involves inositol 1,4,5-triphosphate production in human platelets. Life Sci.62:705-713. [DOI] [PubMed] [Google Scholar]
  67. Jalonen, T. O., Charniga, C. J., and Wielt, D. B. (1997). Beta-amyloid peptide-induced morphological changes coincide with increased K+ and Cl− channel activity in rat cortical astrocytes. Brain Res.746:85-97. [DOI] [PubMed] [Google Scholar]
  68. James, J. H., Wagner, K. R., King, J. K., Leffler, R. E., Upputuri, R. K., Balasubramaniam, A., Friend, L. A., Shelly, D. A., Paul, R. J., and Fischer, J. E. (1999). Stimulation of both aerobic glycolysis and Na+-K+-ATPase activity in skeletal muscle by epinephrine or amylin. Am. J. Physiol.277:E176-E186. [DOI] [PubMed] [Google Scholar]
  69. Jarrett, J. T., and Lansbury, P. T. Jr., (1992). Amyloid fibril formation requires a chemically discriminating nucleation event: Studies of an amyloidogenic sequence from the bacterial protein Osm B. Biochemistry31:12345-12352. [DOI] [PubMed] [Google Scholar]
  70. Kawahara, M., Arispe, N., Kuroda, Y., and Rojas, E. (1997). Alzheimer's disease amyloid β-protein forms Zn2+-sensitive, cation-selective channels across excised membrane patches from hypothalamic neurons. Biophys. J.73:67-75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Keller, J. N., Germeyer, A., Begley, J. G., and Mattson, M. P. (1997a). 17β-Estradiol attenuates oxidative impairment of synaptic Na+/K+-ATPase activity, glucose transport, and glutamate transport induced by amyloid beta-peptide and iron. J. Neurosci. Res.50:522-530. [DOI] [PubMed] [Google Scholar]
  72. Keller, J. N., Pang, Z., Geddes, J. W., Begley, J. G., Germeyer, A., Waeg, G., and Mattson, M. P. (1997b). Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide—Role of the lipid peroxidation product 4-hydroxynonenal. J. Neurochem.69:273-284. [DOI] [PubMed] [Google Scholar]
  73. Kim, C. S., Han, Y. F., Etcheberrigaray, R., Nelson, T. J., Olds, J. L., Yoshioka, T., and Alkon, D. L. (1995). Alzheimer and beta-amyloid-treated fibroblasts demonstrate a decrease in a memory-associated GTP-binding protein, Cp20. Proc. Natl. Acad. Sci. USA92:3060-3064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Kim, H. S., Lee, J. H., and Suh, Y. H. (1999a). C-terminal fragment of Alzheimer's amyloid precursor protein inhibits sodium/calcium exchanger activity in SK-N-SH cell. Neuroreport10:113-116. [DOI] [PubMed] [Google Scholar]
  75. Kim, H. S., Park, C. H., and Suh, Y. H. (1998). C-terminal fragment of amyloid precursor protein inhibits calcium uptake into rat brain microsomes by Mg2+/Ca2+ ATPase. Neuroreport9:3875-3879. [DOI] [PubMed] [Google Scholar]
  76. Kim, H. J., Suh, Y. H., Lee, M. H., and Ryu, P. D. (1999b). Cation selective channels formed by a C-terminal fragment of beta-amyloid precursor protein. Neuroreport10:1427-1431. [DOI] [PubMed] [Google Scholar]
  77. Kourie, J. I. (1997). A redox O2 sensor modulates the SR Ca2+ countercurrent through voltage-and Ca2+-dependent Cl− channels. Am. J. Physiol.272:C324-C332. [DOI] [PubMed] [Google Scholar]
  78. Kourie, J. I. (1998). Interaction of reactive oxygen species with ion transport mechanisms. Am. J. Physiol.275:C1-C24. [DOI] [PubMed] [Google Scholar]
  79. Kourie, J. I. (1999a). Hydrogen peroxide inhibits chloride channels of the sarcoplasmic reticulum of skeletal muscle. J. Membrane Biol.172:25-36. [DOI] [PubMed] [Google Scholar]
  80. Kourie, J. I. (1999b). Synthetic C-type Natriuretic Peptide forms large cation selective channels. FEBS Lett.445:57-62. [DOI] [PubMed] [Google Scholar]
  81. Kourie, J. I. (1999c). Characterisation of a C-type natriuretic peptide CNP-39-formed cation-selective channel from platypus Ornithrorhynchus anatinus venom. J. Physiol. Lond.518:359-369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Kourie, J. I. (1999d). Calcium dependence of C-type natriuretic peptide-formed K+ channel. Am. J. Physiol.277:C43-C50. [DOI] [PubMed] [Google Scholar]
  83. Kourie, J. I., and Culverson, A. (2000). Prion fragment PrP[106–126] forms distinct channel types. J. Neurosci. Res.62:120-133. [DOI] [PubMed] [Google Scholar]
  84. Kourie, J. I., and Rive, R. (1998). The role of natriuretic peptides in ion transport mechanisms. Med. Res. Rev.19:75-94. [DOI] [PubMed] [Google Scholar]
  85. Kourie, J. I., and Shorthouse, A. A. (2000). Properties of cytotoxic peptide-formed ion channels. Am. J. Physiol.278:C1063-C1087. [DOI] [PubMed] [Google Scholar]
  86. Kreutter, D. K., Orena, S. J., Torchia, A. J., Contillo, L. G., Andrews, G. C., and Stevenson, R. W. (1993). Amylin and CGRP induce insulin resistance via a receptor distinct from cAMP-coupled CGRP receptor. Am. J. Physiol.264:E606-613. [DOI] [PubMed] [Google Scholar]
  87. Li, W. Y., Butler, J. P., Hale, J. E., McClure, D. B., Little, S. P., Czilli, D. L., and Simmons, L. K. (2000). Suppression of an amyloid beta peptide-mediated calcium channel response by a secreted beta-amyloid precursor protein. Neuroscience95:1-4. [DOI] [PubMed] [Google Scholar]
  88. Li, S., Mallory, M., Alford, M., Tanaka, S., and Masliah, E. (1997). Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression. J. Neuropathol. Exp. Neurol.56:901-911. [DOI] [PubMed] [Google Scholar]
  89. Lin, H., Zhu, Y. J., and Lal, R. (1999). Amyloid beta protein (1–40) forms calcium-permeable, Zn2+-sensitive channel in reconstituted lipid vesicles. Biochemistry38:11189-11196. [DOI] [PubMed] [Google Scholar]
  90. Lovell, M. A., Xie, C., and Markesbery, W. R. (1999). Protection against amyloid beta peptide toxicity by zinc. Brain Res.823:88-95. [DOI] [PubMed] [Google Scholar]
  91. MacManus, A., Ramsden, M., Murray, M., Henderson, Z., Pearson, H. A., and Campbell, V. A. (2000). Enhancement of 45Ca2+ influx and voltage-dependent Ca2+ channel activity by beta-amyloid-(1–40) in rat cortical synaptosomes and cultured cortical neurons. Modulation by the proinflammatory cytokine interleukin-1beta. J. Biol. Chem.275:4713-4718. [DOI] [PubMed] [Google Scholar]
  92. Mark, R. J., Hensley, K., Butterfield, D. A., and Mattson, M. P. (1995). Amyloid beta-peptide impairs ion-motive ATPase activities: Evidence for a role in loss of neuronal Ca2+ homeostasis and cell death. J. Neurosci.15:6239-6249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Mark, R. J., Keller, J. N., Kruman, I., and Mattson, M. P. (1997a). Basic FGF attenuates amyloid beta-peptide-induced oxidative stress, mitochondrial dysfunction, and impairment of Na+/K+-ATPase activity in hippocampal neurons. Brain Res.756:205-214. [DOI] [PubMed] [Google Scholar]
  94. Mark, R. J., Lovell, M. A., Markesbery, W. R., Uchida, K., and Mattson, M. P. (1997b). A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J. Neurochem.68:255-264. [DOI] [PubMed] [Google Scholar]
  95. Mark, R. J., Pang, Z., Geddes, J. W., Uchida, K., and Mattson, M. P. (1997c). Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: Involvement of membrane lipid peroxidation. J. Neurosci.17:1046-1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Masliah, E., Alford, M., De Teresa, R., Mallory, M., and Hansen, L. (1996). Deficient glutamate transport is associated with neurodegeneration in Alzheimer's disease. Ann. Neurol.40:759-766. [DOI] [PubMed] [Google Scholar]
  97. Masliah, E., Alford, M., Mallory, M., Rockenstein, E., Moechars, D., and Van Leuven, F. (2000). Abnormal glutamate transport function in mutant amyloid precursor protein transgenic mice. Exp. Neurol.163:381-387. [DOI] [PubMed] [Google Scholar]
  98. Masliah, E., Mallory, M., Alford, M., Tanaka, S., and Hansen, L. A. (1998). Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer disease. J. Neuropathol. Exp. Neurol.57:1041-1052. [DOI] [PubMed] [Google Scholar]
  99. Mason, R. P., Shoemaker, W. J., Shajenko, L., and Herbette, L. G. (1993). X-ray diffraction analysis of brain lipid membrane structure in Alzheimer's disease and beta-amyloid peptide interactions. Ann. NY Acad. Sci.695:54-58. [DOI] [PubMed] [Google Scholar]
  100. Mattson, M. P. (1997). Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol. Rev.77:1081-10132. [DOI] [PubMed] [Google Scholar]
  101. Mattson, M. P. (1999). Impairment of membrane transport and signal transduction systems by amyloidogenic proteins. Methods Enzymol.309:733-746. [DOI] [PubMed] [Google Scholar]
  102. Mattson, M. P., Begley, J. G., Mark, R. J., and Furukawa, K. (1997). Aβ25–35 induces rapid lysis of red blood cells: contrast with Aβ1–42 and examination of underlying mechanisms. Brain Res.771:147-153. [DOI] [PubMed] [Google Scholar]
  103. Mattson, M. P., Guo, Q., Furukawa, K., and Pedersen, W. A. (1998). Presenilins, the endoplasmic reticulum, and neuronal apoptosis in Alzheimer's disease. J. Neurochem.70:1-14. [DOI] [PubMed] [Google Scholar]
  104. Mattson, M. P., and Pedersen, W. A. (1998). Effects of APP derivatives and oxidative stress on basal forebrain cholinergic systems in Alzheimer's disease. Int. J. Dev. Neurosci.16:737-753. [DOI] [PubMed] [Google Scholar]
  105. Mattson, M. P., Pedersen, W. A., Duan, W., Culmsee, C., and Camandola, S. (1999). Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases. Ann. NY Acad. Sci.893:154-175. [DOI] [PubMed] [Google Scholar]
  106. McCarty, M. F. (1998). Vascular nitric oxide may lessen Alzheimer's risk. Med. Hypoth.51:465-476. [DOI] [PubMed] [Google Scholar]
  107. Mirzabekov, T., Lin, M., Yuan, W., Marshall, P. J., Carman, M., Tomaselli, K., Lieberburg, I., and Kagan, B. (1994). Channel formation in planar lipid bilayers by a neurotoxic fragment of the beta-amyloid peptide. Biochem. Biophys. Res. Commun.202:1142-1148. [DOI] [PubMed] [Google Scholar]
  108. Mok, S. S., Clippingdale, A. B., Beyreuther, K., Masters, C. L., Barrow, C. J., and Small, D. H. (2000). A beta peptides and calcium influence secretion of the amyloid protein precursor from chick sympathetic neurons in culture. J. Neurosci. Res.61:449-457. [DOI] [PubMed] [Google Scholar]
  109. Morimoto, T., Ohsawa, I., Takamura, C., Ishiguro, M., Nakamura, Y., and Kohsaka, S. (1998). Novel domain-specific actions of amyloid precursor protein on developing synapses. J. Neurosci.18:9386-9393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Murphy, M. P., Hickman, L. J., Eckman C. B., Uljon S. N., Wang, R., and Golde, T. E. (1999). Gamma-secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid beta peptides of varying length. J. Biol. Chem.274:11914-11923. [DOI] [PubMed] [Google Scholar]
  111. Murphy, M. P., Uljon, S. N., Fraser, P. E., Fauq, A., Lookingbill, H. A., Findlay, K. A., Smith, T. E., Lewis, P. A., McLendon, D. C., Wang, R., and Golde, T. E. (2000). Presenilin 1 regulates pharmacologically distinct gamma-secretase activities. Implications for the role of presenilin in gamma-secretase cleavage. J. Biol. Chem.275:26277-26284. [DOI] [PubMed] [Google Scholar]
  112. Nitsch, R. M., Farber, S. A., Growdon, J. H., and Wurtman, R. J. (1993). Release of amyloid β-protein precursor derivatives by electrical depolarization of rat hippocampal slices. Proc. Natl. Acad. Sci. USA90:5191-5193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Noda, M., Nakanishi, H., and Akaike, N. (1999). Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide. Neuroscience92:1465-1474. [DOI] [PubMed] [Google Scholar]
  114. Paris, D., Town, T., Parker, T. A., Tan, J., Humphrey, J., Crawford, F., and Mullan, M. (1999). Inhibition of Alzheimer's beta-amyloid induced vasoactivity and proinflammatory response in microglia by a cGMP-dependent mechanism. Exp. Neurol.157:211-221. [DOI] [PubMed] [Google Scholar]
  115. Pike, C. J., Burdick, D., Walencewicz, A. J., Glabe, C. G., and Cotman, C. W. (1993). Neurodegeneration induced by beta-amyloid peptides in vitro: The role of peptide assembly state. J. Neurosci.13:1676-1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Pike, C. J., Walencewicz, A. J., Glabe, C. G., and Cotman, C. W. (1991a). In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res.563:311-314. [DOI] [PubMed] [Google Scholar]
  117. Pike, C. J., Walencewicz, A. J., Glabe, C. G., and Cotman, C. W. (1991b). Aggregation-related toxicity of synthetic beta-amyloid protein in hippocampal cultures. Eur. J. Pharmacol.207:367-368. [DOI] [PubMed] [Google Scholar]
  118. Pittner, R. A., Wolfe-Lopez, D., Young, A. A., and Rink, T. J. (1995). Amylin and epinephrine have no direct effect on glucose transport in isolated rat soleus muscle. FEBS Lett.365:98-100. [DOI] [PubMed] [Google Scholar]
  119. Pollard, H. B., Arispe, N., and Rojas, E. (1995). Ion channel hypothesis for Alzheimer amyloid peptide neurotoxicity. Cell Mol. Neurobiol.15:513-526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Pollard, H. B., Rojas, E., and Arispe, N. (1993). A new hypothesis for the mechanism of amyloid toxicity, based on the calcium channel activity of amyloid beta protein (AβP) in phospholipid bilayer membranes. Ann. NY Acad. Sci.695:165-168. [DOI] [PubMed] [Google Scholar]
  121. Price, S. A., Held, B., and Pearson, H. A. (1998). Amyloid beta protein increases Ca2+ currents in rat cerebellar granule neurones. Neuroreport9:539-545. [PubMed] [Google Scholar]
  122. Rhee, S. K., Quist, A. P., and Lal, R. (1998). Amyloid beta protein-(1–42) forms calcium-permeable, Zn2+-sensitive channel. J. Biol. Chem.273:13379-13382. [DOI] [PubMed] [Google Scholar]
  123. Sanderson, K. L., Butler, L., and Ingram, V. M. (1997). Aggregates of a beta-amyloid peptide are required to induce calcium currents in neuron-like human teratocarcinoma cells: Relation to Alzheimer's disease. Brain Res.744:7-14. [DOI] [PubMed] [Google Scholar]
  124. Sawada, M., and Ichinose, M. (1996). Amyloid beta proteins reduce the GABA-induced Cl− current in identified Aplysia neurons. Neurosci. Lett.213:213-215. [DOI] [PubMed] [Google Scholar]
  125. Schubert, D., Behl, C., Lesley, R., Brack, A., Dargusch, R., Sagara, Y., and Kimura, H. (1995). Amyloid peptides are toxic via a common oxidative mechanism. Proc. Natl. Acad. Sci. USA92:1989-1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Shattock, M. J., and Matsuura, H. (1993). Measurement of Na+-K+ pump current in isolated rabbit ventricular myocytes using the whole-cell voltage-clamp technique. Inhibition of the pump by oxidant stress. Circ. Res.72:91-101. [DOI] [PubMed] [Google Scholar]
  127. Silei, V., Fabrizi, C., Venturini, G., Salmona, M., Bugiani, O., Tagliavini, F., and Lauro, G. M. (1999). Activation of microglial cells by PrP and beta-amyloid fragments raises intracellular calcium through L-type voltage sensitive calcium channels. Brain Res.818:168-170. [DOI] [PubMed] [Google Scholar]
  128. Simmons, M. A., and Schneider, C. R. (1993). Amyloid β peptides act directly on single neurons. Neurosci. Lett.150:133-136. [DOI] [PubMed] [Google Scholar]
  129. Sipe, J. D. (1994). Amyloidosis. Crit. Rev. Clin. Lab. Sci.31:325-354. [DOI] [PubMed] [Google Scholar]
  130. St George-Hyslop, P. H. (2000). Molecular genetics of Alzheimer's disease. Biol. Psychiatry47:183-199. [DOI] [PubMed] [Google Scholar]
  131. St George-Hyslop, P. H., Haines, J. L., Farrer, L. A., Polinsky, R., Broeckhoven, C. V., Goate, A., Crapper McLachlan, D. R., Orr, H., Bruni, A. C., Sorbi, S., Rainero, I., Foncin, J. F., Pollen, D., Cantu, J. M., Tupler, R., Voskresenskaya, N., Mayeux, R., Growdon, J., Fried, V. A., Myers, R. H., Nee, L., Backhovens, H., Martin, J. J., Rossor, M., Owen, M. J., Mullan, M., Percy, M. E., Karlinsky, H., Rich, S., Heston, L., Montesi, M., Mortilla, M., Nacmias, N., Gusella, J. F., and Hardy, J. A. (1990). Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder. Nature347:194-197. [DOI] [PubMed] [Google Scholar]
  132. Strosznajder, J. B., Zambrzycka, A., Kacprzak, M. D., and Strosznajder, R. P. (1999). Amyloid beta peptide 25–35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex. J. Mol. Neurosci.12:101-109. [DOI] [PubMed] [Google Scholar]
  133. Takenouchi, T., and Munekata, E. (1998). Amyloid beta-peptide-induced inhibition of MTT reduction in PC12h and C1300 neuroblastoma cells: Effect of nitroprusside. Peptides19:365-372. [DOI] [PubMed] [Google Scholar]
  134. Vargas, J., Alarcon, J. M., and Rojas, E. (2000). Displacement currents associated with the insertion of Alzheimer disease amyloid beta-peptide into planar bilayer membranes. Biophys. J. 2000 79:934-944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  135. Ueda, K., Shinohara, S., Yagami, T., Asakura, K., and Kawasaki, K. (1997). Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: A possible involvement of free radicals. J. Neurochem.68:265-271. [DOI] [PubMed] [Google Scholar]
  136. Weiss, J. H., Pike, C. J., and Cotman, C. W. (1994). Ca2+ channel blockers attenuate beta-amyloid peptide toxicity to cortical neurons in culture. J. Neurochem.62:372-375. [DOI] [PubMed] [Google Scholar]
  137. Whitson, J. S., and Appel, S. H. (1995). Neurotoxicity of Aβ amyloid protein in vitro is not altered by calcium channel blockade. Neurobiol. Aging16:5-10. [DOI] [PubMed] [Google Scholar]
  138. Wu, J., Anwyl, R., and Rowan, M. J. (1995). Beta-Amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus. Neuroreport6:2409-2413. [DOI] [PubMed] [Google Scholar]
  139. Yu, S. P., Farhangrazi, Z. S., Ying, H. S., Yeh, C. H., and Choi, D. W. (1998). Enhancement of outward potassium current may participate in beta-amyloid peptide-induced cortical neuronal death. Neurobiol. Dis.5:81-88. [DOI] [PubMed] [Google Scholar]
  140. Zhou, Y., Gopalakrishnan, V., and Richardson, J. S. (1996). Actions of neurotoxic beta-amyloid on calcium homeostasis and viability of PC12 cells are blocked by antioxidants but not by calcium channel antagonists. J. Neurochem.67:1419-1425. [DOI] [PubMed] [Google Scholar]
  141. Zierath, J. R., Galuska, D., Engstrom, A., Johnson, K. H., Betsholtz, C., Westermark, P., and Wallberg-Henriksson, H. (1992). Human islet amyloid polypeptide at pharmacological levels inhibits insulin and phorbol ester-stimulated glucose transport in in vitro incubated human muscle strips. Diabetologia35:26-31. [DOI] [PubMed] [Google Scholar]

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