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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 857368, 7 pages
http://dx.doi.org/10.4061/2011/857368
Review Article

Protein Kinase C-Regulated Aβ Production and Clearance

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

Received 13 October 2010; Revised 3 December 2010; Accepted 13 December 2010

Academic Editor: Katsuhiko Yanagisawa

Copyright © 2011 Taehyun Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. J. Selkoe, “Alzheimer's disease: genes, proteins, and therapy,” Physiological Reviews, vol. 81, no. 2, pp. 741–766, 2001. View at Google Scholar · View at Scopus
  2. R. A. Sperling, B. C. Dickerson, M. Pihlajamaki et al., “Functional alterations in memory networks in early alzheimer's disease,” NeuroMolecular Medicine, vol. 12, no. 1, pp. 27–43, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. E. Marcello, R. Epis, and M. Di Luca, “Amyloid flirting with synaptic failure: towards a comprehensive view of Alzheimer's disease pathogenesis,” European Journal of Pharmacology, vol. 585, no. 1, pp. 109–118, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Gabelle, S. Roche, C. Gény et al., “Correlations between soluble α/β forms of amyloid precursor protein and Aβ38, 40, and 42 in human cerebrospinal fluid,” Brain Research, vol. 1357, pp. 175–183, 2010. View at Publisher · View at Google Scholar
  5. B. De Strooper, M. Simons, G. Multhaup, F. Van Leuven, K. Beyreuther, and C. G. Dotti, “Production of intracellular amyloid-containing fragments in hippocampal neurons expressing human amyloid precursor protein and protection against amyloidogenesis by subtle amino acid substitutions in the rodent sequence,” The EMBO Journal, vol. 14, no. 20, pp. 4932–4938, 1995. View at Google Scholar · View at Scopus
  6. M. E. Fortini, “γ-secretase-mediated proteolysis in cell-surface-receptor signalling,” Nature Reviews Molecular Cell Biology, vol. 3, no. 9, pp. 673–684, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. P. Tiraboschi, L. A. Hansen, L. J. Thal, and J. Corey-Bloom, “The importance of neuritic plaques and tangles to the development and evolution of AD,” Neurology, vol. 62, no. 11, pp. 1984–1989, 2004. View at Google Scholar · View at Scopus
  8. L. Mucke, E. Masliah, G. Q. Yu et al., “High-level neuronal expression of Aβ142 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation,” Journal of Neuroscience, vol. 20, no. 11, pp. 4050–4058, 2000. View at Google Scholar · View at Scopus
  9. G. V. W. Johnson and W. H. Stoothoff, “Tau phosphorylation in neuronal cell function and dysfunction,” Journal of Cell Science, vol. 117, no. 24, pp. 5721–5729, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. L. M. Ittner, Y. D. Ke, F. Delerue et al., “Dendritic function of tau mediates amyloid-β toxicity in alzheimer's disease mouse models,” Cell, vol. 142, no. 3, pp. 387–397, 2010. View at Publisher · View at Google Scholar
  11. M. S. Wolfe, “Selective amyloid-β lowering agents,” BMC Neuroscience, vol. 9, no. 2, article S4, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. J. Neugroschl and M. Sano, “An update on treatment and prevention strategies for Alzheimer's disease,” Current Neurology and Neuroscience Reports, vol. 9, no. 5, pp. 368–376, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. G. He, W. Luo, P. Li et al., “Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease,” Nature, vol. 467, no. 7311, pp. 95–98, 2010. View at Publisher · View at Google Scholar
  14. D. S. Choi, D. Wang, G. Q. Yu et al., “PKCε increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 21, pp. 8215–8220, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. G. Zhu, D. Wang, Y.-H. Lin, T. McMahon, E. H. Koo, and R. O. Messing, “Protein kinase C ε suppresses Aβ production and promotes activation of α-secretase,” Biochemical and Biophysical Research Communications, vol. 285, no. 4, pp. 997–1006, 2001. View at Publisher · View at Google Scholar
  16. E. A. Eckman and C. B. Eckman, “Aβ-degrading enzymes: modulators of Alzheimer's disease pathogenesis and targets for therapeutic intervention,” Biochemical Society Transactions, vol. 33, no. 5, pp. 1101–1105, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. B. De Strooper, R. Vassar, and T. Golde, “The secretases: enzymes with therapeutic potential in Alzheimer disease,” Nature Review Neurology, vol. 6, pp. 99–107, 2010. View at Google Scholar
  18. Y. Nishizuka, “Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C,” Science, vol. 258, no. 5082, pp. 607–614, 1992. View at Google Scholar · View at Scopus
  19. J. Hofmann, “The potential for isoenzyme-selective modulation of protein kinase C,” FASEB Journal, vol. 11, no. 8, pp. 649–669, 1997. View at Google Scholar · View at Scopus
  20. H. Mellor and P. J. Parker, “The extended protein kinase C superfamily,” Biochemical Journal, vol. 332, no. 2, pp. 281–292, 1998. View at Google Scholar · View at Scopus
  21. J. D. Buxbaum, M. Oishi, H. I. Chen et al., “Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer β/A4 amyloid protein precursor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 21, pp. 10075–10078, 1992. View at Publisher · View at Google Scholar · View at Scopus
  22. A. Y. Hung, C. Haass, R. M. Nitsch et al., “Activation of protein kinase C inhibits cellular production of the amyloid β-protein,” The Journal of Biological Chemistry, vol. 268, no. 31, pp. 22959–22962, 1993. View at Google Scholar · View at Scopus
  23. M. J. Savage, S. P. Trusko, D. S. Howland et al., “Turnover of amyloid β-protein in mouse brain and acute reduction of its level by phorbol ester,” Journal of Neuroscience, vol. 18, no. 5, pp. 1743–1752, 1998. View at Google Scholar · View at Scopus
  24. H. Fu, J. Dou, W. Li et al., “Promising multifunctional anti-Alzheimer's dimer bis(7)-Cognitin acting as an activator of protein kinase C regulates activities of α-secretase and BACE-1 concurrently,” European Journal of Pharmacology, vol. 623, no. 1-3, pp. 14–21, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. T. Kinouchi, H. Sorimachi, K. Maruyama et al., “Conventional protein kinase C (PKC)-α and novel PKCε, but not -δ, increase the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein from PKC cDNA transfected 3Y1 fibroblasts,” FEBS Letters, vol. 364, no. 2, pp. 203–206, 1995. View at Publisher · View at Google Scholar
  26. C. Jolly-Tornetta and B. A. Wolf, “Regulation of amyloid precursor protein (APP) secretion by protein kinase Cα in human Ntera 2 neurons (NT2N),” Biochemistry, vol. 39, no. 25, pp. 7428–7435, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. S. W. Yeon, M W. Jung, M. J. Ha et al., “Blockade of PKCε activation attenuates phorbol ester-induced increase of α-secretase-derived secreted form of amyloid precursor protein,” Biochemical and Biophysical Research Communications, vol. 280, no. 3, pp. 782–787, 2001. View at Publisher · View at Google Scholar
  28. M. J. Savage, S. P. Trusko, D. S. Howland et al., “Turnover of amyloid β-protein in mouse brain and acute reduction of its level by phorbol ester,” Journal of Neuroscience, vol. 18, no. 5, pp. 1743–1752, 1998. View at Google Scholar · View at Scopus
  29. D. J. Selkoe and D. Schenk, “Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics,” Annual Review of Pharmacology and Toxicology, vol. 43, pp. 545–584, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. D. J. Selkoe, “Clearing the brain's amyloid cobwebs,” Neuron, vol. 32, no. 2, pp. 177–180, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. W. C. Duckworth, R. G. Bennett, and F. G. Hamel, “Insulin degradation: progress and potential,” Endocrine Reviews, vol. 19, no. 5, pp. 608–624, 1998. View at Publisher · View at Google Scholar · View at Scopus
  32. K. Vekrellis, Z. Ye, W. Q. Qiu et al., “Neurons regulate extracellular levels of amyloid β-protein via proteolysis by insulin-degrading enzyme,” Journal of Neuroscience, vol. 20, no. 5, pp. 1657–1665, 2000. View at Google Scholar · View at Scopus
  33. A. Mukherjee, E. S. Song, M. Kihiko-Ehmann et al., “Insulysin hydrolyzes amyloid β peptides to products that are neither neurotoxic nor deposit on amyloid plaques,” Journal of Neuroscience, vol. 20, no. 23, pp. 8745–8749, 2000. View at Google Scholar · View at Scopus
  34. W. Farris, S. Mansourian, Y. Chang et al., “Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 7, pp. 4162–4167, 2003. View at Publisher · View at Google Scholar
  35. N. Iwata, S. Tsubuki, Y. Takaki et al., “Identification of the major Aβ-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition,” Nature Medicine, vol. 6, no. 2, pp. 143–150, 2000. View at Publisher · View at Google Scholar · View at Scopus
  36. K. Barnes, A. J. Turner, and A. J. Kenny, “Membrane localization of endopeptidase-24.11 and peptidyl dipeptidase A (angiotensin converting enzyme) in the pig brain: a study using subcellular fractionation and electron microscopic immunocytochemistry,” Journal of Neurochemistry, vol. 58, no. 6, pp. 2088–2096, 1992. View at Publisher · View at Google Scholar · View at Scopus
  37. N. Iwata, S. Tsubuki, Y. Takaki et al., “Metabolic regulation of brain Aβ by neprilysin,” Science, vol. 292, no. 5521, pp. 1550–1552, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. M. A. Leissring, W. Farris, A. Y. Chang et al., “Enhanced proteolysis of β-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death,” Neuron, vol. 40, no. 6, pp. 1087–1093, 2003. View at Publisher · View at Google Scholar
  39. J. L. Guy, D. W. Lambert, F. J. Warner, N. M. Hooper, and A. J. Turner, “Membrane-associated zinc peptidase families: comparing ACE and ACE2,” Biochimica et Biophysica Acta, vol. 1751, no. 1, pp. 2–8, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. B. Rigat, C. Hubert, F. Alhenc-Gelas, F. Cambien, P. Corvol, and F. Soubrier, “An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels,” The Journal of Clinical Investigation, vol. 86, no. 4, pp. 1343–1346, 1990. View at Google Scholar · View at Scopus
  41. M. L. Hemming and D. J. Selkoe, “Amyloid β-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor,” The Journal of Biological Chemistry, vol. 280, no. 45, pp. 37644–37650, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. R. E. Tanzi, R. D. Moir, and S. L. Wagner, “Clearance of Alzheimer's Aβ peptide: the many roads to perdition,” Neuron, vol. 43, no. 5, pp. 605–608, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. B. V. Zlokovic, “Clearing amyloid through the blood-brain barrier,” Journal of Neurochemistry, vol. 89, no. 4, pp. 807–811, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. A. J. Turner and L. J. Murphy, “Molecular pharmacology of endothelin converting enzymes,” Biochemical Pharmacology, vol. 51, no. 2, pp. 91–102, 1996. View at Publisher · View at Google Scholar · View at Scopus
  45. B. Funalot, T. Ouimet, A. Claperon et al., “Endothelin-converting enzyme-1 is expressed in human cerebral cortex and protects against Alzheimer's disease,” Molecular Psychiatry, vol. 9, no. 12, p. 1059, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. H. Yanagisawa, R. E. Hammer, J. A. Richardson et al., “Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development,” The Journal of Clinical Investigation, vol. 105, no. 10, pp. 1373–1382, 2000. View at Google Scholar · View at Scopus
  47. P. Korth, R. M. Bohle, P. Corvol, and F. Pinet, “Cellular distribution of endothelin-converting enzyme-1 in human tissues,” Journal of Histochemistry and Cytochemistry, vol. 47, no. 4, pp. 447–461, 1999. View at Google Scholar · View at Scopus
  48. J. M. Sluck, R. C. S. Lin, L. I. Katolik, A. Y. Jeng, and J. C. Lehmann, “Endothelin converting enzyme-1-, endothelin-1-, and endothelin-3-like immunoreactivity in the rat brain,” Neuroscience, vol. 91, no. 4, pp. 1483–1497, 1999. View at Publisher · View at Google Scholar · View at Scopus
  49. E. A. Eckman, D. K. Reed, and C. B. Eckman, “Degradation of the Alzheimer's amyloid β peptide by endothelin-converting enzyme,” The Journal of Biological Chemistry, vol. 276, no. 27, pp. 24540–24548, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. E. A. Eckman, M. Watson, L. Marlow, K. Sambamurti, and C. B. Eckman, “Alzheimer's disease β-amyloid peptide is increased in mice deficient in endothelin-converting enzyme,” The Journal of Biological Chemistry, vol. 278, no. 4, pp. 2081–2084, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. E. A. Eckman, S. K. Adams, F. J. Troendle et al., “Regulation of steady-state β-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme,” The Journal of Biological Chemistry, vol. 281, no. 41, pp. 30471–30478, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. J. C. Palmer, S. Baig, P. G. Kehoe, and S. Love, “Endothelin-converting enzyme-2 is increased in Alzheimer's disease and up-regulated by Aβ,” American Journal of Pathology, vol. 175, no. 1, pp. 262–270, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. V. Naidoo, S. Naidoo, R. Mahabeer, and D. M. Raidoo, “Cellular distribution of the endothelin system in the human brain,” Journal of Chemical Neuroanatomy, vol. 27, no. 2, pp. 87–98, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Minami, M. Kimura, N. Iwamoto, and H. Arai, “Endothelin-1-like immunoreactivity in cerebral cortex of Alzheimer-type dementia,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 19, no. 3, pp. 509–513, 1995. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Luo and P. Grammas, “Endothelin-1 is elevated in Alzheimer's disease brain microvessels and is neuroprotective,” Journal of Alzheimer's Disease, vol. 21, no. 3, pp. 887–896, 2010. View at Publisher · View at Google Scholar
  56. M. Arundine and M. Tymianski, “Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity,” Cell Calcium, vol. 34, no. 4-5, pp. 325–337, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. M. K. Sun, J. Hongpaisan, T. J. Nelson, and D. L. Alkon, “Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 36, pp. 13620–13625, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Etcheberrigaray, L. D. Matzel, I. I. Lederhendler, and D. L. Alkon, “Classical conditioning and protein kinase C activation regulate the same single potassium channel in Hermissenda crassicornis photoreceptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 15, pp. 7184–7188, 1992. View at Publisher · View at Google Scholar · View at Scopus
  59. O. A. B. da Cruz E Silva, S. Rebelo, S. I. Vieira, S. Gandy, E. F. da Cruz E Silva, and P. Greengard, “Enhanced generation of Alzheimer's amyloid-β following chronic exposure to phorbol ester correlates with differential effects on alpha and epsilon isozymes of protein kinase C,” Journal of Neurochemistry, vol. 108, no. 2, pp. 319–330, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. S. B. Roberts, J. A. Ripellino, K. M. Ingalls, N. K. Robakis, and K. M. Felsenstein, “Non-amyloidogenic cleavage of the β-amyloid precursor protein by an integral membrane metalloendopeptidase,” The Journal of Biological Chemistry, vol. 269, no. 4, pp. 3111–3116, 1994. View at Google Scholar · View at Scopus
  61. S. Bandyopadhyay, D. M. Hartley, C. M. Cahill, D. K. Lahiri, N. Chattopadhyay, and J. T. Rogers, “Interleukin-1α stimulates non-amyloidogenic pathway by α-secretase (ADAM-10 and ADAM-17) cleavage of APP in human astrocytic cells involving p38 MAP kinase,” Journal of Neuroscience Research, vol. 84, no. 1, pp. 106–118, 2006. View at Publisher · View at Google Scholar
  62. M. Racchi, M. Mazzucchelli, A. Pascale, M. Sironi, and S. Govoni, “Role of protein kinase Cα in the regulated secretion of the amyloid precursor protein,” Molecular Psychiatry, vol. 8, no. 2, pp. 209–216, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. J. D. Buxbaum, E. H. Koo, and P. Greengard, “Protein phosphorylation inhibits production of Alzheimer amyloid β/A4 peptide,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 19, pp. 9195–9198, 1993. View at Publisher · View at Google Scholar · View at Scopus
  64. J. Mills, D. L. Charest, F. Lam et al., “Regulation of amyloid precursor protein catabolism involves the mitogen-activated protein kinase signal transduction pathway,” Journal of Neuroscience, vol. 17, no. 24, pp. 9415–9422, 1997. View at Google Scholar · View at Scopus
  65. C. E. Foulds, M. L. Nelson, A. G. Blaszczak, and B. J. Graves, “Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment,” Molecular and Cellular Biology, vol. 24, no. 24, pp. 10954–10964, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. A. D. Sharrocks, “The ETS-domain transcription factor family,” Nature Reviews Molecular Cell Biology, vol. 2, no. 11, pp. 827–837, 2001. View at Publisher · View at Google Scholar · View at Scopus
  67. V. I. Sementchenko and D. K. Watson, “Ets target genes: past, present and future,” Oncogene, vol. 19, no. 55, pp. 6533–6548, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. T. Nakano, M. Abe, K. Tanaka, R. Shineha, S. Satomi, and Y. Sato, “Angiogenesis inhibition by transdominant mutant Ets-1,” Journal of Cellular Physiology, vol. 184, no. 2, pp. 255–262, 2000. View at Publisher · View at Google Scholar · View at Scopus
  69. P. Helguera, A. Pelsman, G. Pigino, E. Wolvetang, E. Head, and J. Busciglio, “ets-2 promotes the activation of a mitochondrial death pathway in down's syndrome neurons,” Journal of Neuroscience, vol. 25, no. 9, pp. 2295–2303, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. Y. J. Wang, H. D. Zhou, and X. F. Zhou, “Clearance of amyloid-beta in Alzheimer's disease: progress, problems and perspectives,” Drug Discovery Today, vol. 11, no. 19-20, pp. 931–938, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. D. M. Skovronsky, D. B. Moore, M. E. Milla, R. W. Doms, and V. M.-Y. Lee, “Protein kinase C-dependent α-secretase competes with β-secretase for cleavage of amyloid-β precursor protein in the trans-Golgi network,” The Journal of Biological Chemistry, vol. 275, no. 4, pp. 2568–2575, 2000. View at Publisher · View at Google Scholar
  72. A. T. Weeraratna, A. Kalehua, I. DeLeon et al., “Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues,” Experimental Cell Research, vol. 313, no. 3, pp. 450–461, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. T. K. Khan, T. J. Nelson, V. A. Verma, P. A. Wender, and D. L. Alkon, “A cellular model of Alzheimer's disease therapeutic efficacy: PKC activation reverses Aβ-induced biomarker abnormality on cultured fibroblasts,” Neurobiology of Disease, vol. 34, no. 2, pp. 332–339, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. T. J. Nelson, C. Cui, Y. Luo, and D. L. Alkon, “Reduction of β-amyloid levels by novel protein kinase Ċactivators,” The Journal of Biological Chemistry, vol. 284, no. 50, pp. 34514–34521, 2009. View at Publisher · View at Google Scholar · View at Scopus