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J Toxicol. 2012;2012:187297. doi: 10.1155/2012/187297. Epub 2012 Feb 08.

Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling.

Journal of toxicology

Mario Nizzari, Stefano Thellung, Alessandro Corsaro, Valentina Villa, Aldo Pagano, Carola Porcile, Claudio Russo, Tullio Florio

Affiliations

  1. Section of Pharmacology, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genova, 16132 Genova, Italy.

PMID: 22496686 PMCID: PMC3306972 DOI: 10.1155/2012/187297

Abstract

Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

References

  1. Genome Res. 2005 Mar;15(3):364-8 - PubMed
  2. Mol Cell Biol. 2001 Mar;21(5):1540-51 - PubMed
  3. J Huazhong Univ Sci Technolog Med Sci. 2011 Aug;31(4):578 - PubMed
  4. Mol Cell Biol. 2005 Nov;25(21):9259-68 - PubMed
  5. J Neurosci Res. 2008 Jun;86(8):1659-69 - PubMed
  6. Am J Pathol. 1999 Nov;155(5):1459-66 - PubMed
  7. Cell. 2007 Oct 19;131(2):215-21 - PubMed
  8. Brain Res Mol Brain Res. 2003 Jan 31;110(1):119-25 - PubMed
  9. Eur Biophys J. 2008 Mar;37(3):315-21 - PubMed
  10. PLoS Genet. 2007 Feb 2;3(2):e1 - PubMed
  11. Ann N Y Acad Sci. 2007 Jan;1096:249-57 - PubMed
  12. Neurodegener Dis. 2007;4(2-3):101-11 - PubMed
  13. Biochem Soc Symp. 1999;64:29-48 - PubMed
  14. J Biol Chem. 2002 Feb 1;277(5):3767-75 - PubMed
  15. Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18367-72 - PubMed
  16. J Clin Invest. 2005 Jun;115(6):1449-57 - PubMed
  17. Pharmacol Ther. 2006 Jul;111(1):99-113 - PubMed
  18. J Neurosci Res. 2001 Feb 1;63(3):257-67 - PubMed
  19. Nature. 1997 Oct 16;389(6652):733-7 - PubMed
  20. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):403-9 - PubMed
  21. Semin Cell Dev Biol. 2009 Apr;20(2):191-200 - PubMed
  22. J Biol Chem. 2005 Nov 4;280(44):36895-904 - PubMed
  23. J Biol Chem. 2002 May 24;277(21):18736-43 - PubMed
  24. J Neurochem. 2005 Apr;93(1):145-55 - PubMed
  25. Life Sci. 2005 Dec 5;78(3):321-8 - PubMed
  26. Neuron. 2004 Apr 8;42(1):23-36 - PubMed
  27. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15938-43 - PubMed
  28. Genes Dev. 2000 Nov 15;14(22):2799-806 - PubMed
  29. Nature. 1992 Sep 24;359(6393):288-94 - PubMed
  30. J Cell Sci. 2000 Jun;113 ( Pt 11):1857-70 - PubMed
  31. Science. 2001 Jul 6;293(5527):115-20 - PubMed
  32. J Biol Chem. 2001 Jun 8;276(23):19787-92 - PubMed
  33. J Alzheimers Dis. 2010;22(1):65-72 - PubMed
  34. Nat Cell Biol. 2008 Mar;10(3):283-94 - PubMed
  35. Cell. 1997 Sep 5;90(5):917-27 - PubMed
  36. J Biol Chem. 1999 Aug 20;274(34):24007-13 - PubMed
  37. J Biol Chem. 2002 Sep 20;277(38):35282-8 - PubMed
  38. J Clin Invest. 2003 Jan;111(1):11-8 - PubMed
  39. J Neurosci. 2006 Jan 18;26(3):775-84 - PubMed
  40. J Alzheimers Dis. 2007 May;11(2):191-205 - PubMed
  41. Science. 2002 Jul 19;297(5580):353-6 - PubMed
  42. Science. 2002 Dec 6;298(5600):1911-2 - PubMed
  43. J Biol Chem. 1995 Dec 29;270(52):30853-6 - PubMed
  44. J Med Genet. 2005 Nov;42(11):857-62 - PubMed
  45. Neurobiol Dis. 2011 Feb;41(2):308-17 - PubMed
  46. Nature. 1995 Aug 31;376(6543):775-8 - PubMed
  47. Nature. 2003 May 22;423(6938):435-9 - PubMed
  48. Annu Rev Genomics Hum Genet. 2002;3:67-99 - PubMed
  49. J Biol Chem. 2004 Jun 4;279(23):24601-11 - PubMed
  50. Neurobiol Aging. 2007 Mar;28(3):377-88 - PubMed
  51. J Biol Chem. 1998 Jun 12;273(24):14761-6 - PubMed
  52. Nature. 2001 Jun 7;411(6838):654-6 - PubMed
  53. J Biol Chem. 1996 May 10;271(19):11339-46 - PubMed
  54. Science. 1993 Aug 13;261(5123):921-3 - PubMed
  55. J Biol Chem. 2003 Mar 14;278(11):9388-93 - PubMed
  56. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10863-8 - PubMed
  57. Biochem Biophys Res Commun. 1993 Jun 15;193(2):639-47 - PubMed
  58. J Neurochem. 2002 Sep;82(6):1480-9 - PubMed
  59. Biochem Biophys Res Commun. 2005 Jul 1;332(2):609-13 - PubMed
  60. Oncogene. 2004 Aug 26;23(39):6684-92 - PubMed
  61. J Neurosci Res. 2003 Oct 15;74(2):184-91 - PubMed
  62. J Cell Biol. 2000 Feb 7;148(3):399-404 - PubMed
  63. J Neurosci. 1999 Mar 1;19(5):1717-27 - PubMed
  64. J Biol Chem. 1997 Mar 7;272(10):6399-405 - PubMed
  65. J Biol Chem. 1996 Apr 5;271(14):8373-80 - PubMed
  66. J Biol Chem. 2006 Feb 10;281(6):3425-31 - PubMed
  67. J Cell Biol. 2001 Jun 25;153(7):1403-14 - PubMed
  68. Nature. 1998 May 28;393(6683):382-6 - PubMed
  69. Nature. 2000 Jun 1;405(6786):531-2 - PubMed
  70. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5093-8 - PubMed
  71. EMBO Rep. 2009 Jan;10(1):94-100 - PubMed
  72. Nat Rev Neurosci. 2009 May;10(5):333-44 - PubMed
  73. EMBO J. 2002 Apr 15;21(8):1948-56 - PubMed
  74. J Biol Chem. 2006 Jun 30;281(26):17670-80 - PubMed
  75. J Cell Biol. 1996 Feb;132(3):413-25 - PubMed
  76. Cell. 2005 Feb 25;120(4):545-55 - PubMed
  77. Mol Psychiatry. 2005 Jun;10(6):522-4 - PubMed
  78. J Neurosci. 2009 Jun 10;29(23):7459-73 - PubMed
  79. Biochem J. 2007 Nov 1;407(3):435-50 - PubMed
  80. Brain Res Rev. 2006 Sep;52(2):305-15 - PubMed
  81. J Biol Chem. 2000 Mar 10;275(10):7410-5 - PubMed
  82. Funct Neurol. 2002 Apr-Jun;17(2):65-70 - PubMed
  83. Genes Dev. 2000 May 15;14(10):1169-80 - PubMed
  84. Science. 1995 Aug 18;269(5226):973-7 - PubMed
  85. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9620-5 - PubMed
  86. N Engl J Med. 2005 Mar 3;352(9):884-94 - PubMed
  87. J Alzheimers Dis. 2004 Apr;6(2):165-9 - PubMed
  88. Brain Res Rev. 2008 Jun;58(1):96-105 - PubMed
  89. EMBO J. 2000 May 15;19(10):2270-9 - PubMed
  90. J Biol Chem. 2001 Oct 26;276(43):40353-61 - PubMed
  91. Immunity. 1999 Dec;11(6):653-63 - PubMed
  92. Oncogene. 2003 Mar 13;22(10):1511-6 - PubMed
  93. Mol Neurodegener. 2007 Jul 09;2:14 - PubMed
  94. J Neurosci. 2001 Apr 15;21(8):2661-8 - PubMed
  95. EMBO J. 1997 Aug 15;16(16):4897-907 - PubMed
  96. Biochem J. 2000 Jun 1;348 Pt 2:359-65 - PubMed
  97. J Biol Chem. 2007 May 4;282(18):13833-44 - PubMed
  98. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5573-8 - PubMed
  99. Nature. 1999 Dec 9;402(6762):615-22 - PubMed
  100. J Neurosci. 2005 Jun 29;25(26):6127-36 - PubMed
  101. Nature. 1998 Oct 15;395(6703):698-702 - PubMed
  102. Nat Biotechnol. 2003 Apr;21(4):379-86 - PubMed
  103. Science. 1999 Apr 30;284(5415):770-6 - PubMed
  104. Cell. 2003 Sep 5;114(5):635-45 - PubMed
  105. Arch Neurol. 2003 Aug;60(8):1149-51 - PubMed
  106. J Neuropathol Exp Neurol. 1999 Sep;58(9):1020-6 - PubMed
  107. J Neurochem. 2002 Aug;82(4):839-47 - PubMed
  108. Ann N Y Acad Sci. 2006 Dec;1090:455-65 - PubMed
  109. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81 - PubMed
  110. Trends Neurosci. 1998 Nov;21(11):476-81 - PubMed
  111. Neurobiol Aging. 2006 Nov;27(11):1632-43 - PubMed
  112. Acta Neuropathol. 2001 Apr;101(4):305-10 - PubMed
  113. Neurobiol Dis. 2003 Nov;14(2):194-204 - PubMed
  114. Exp Brain Res. 2012 Apr;217(3-4):377-87 - PubMed
  115. Nat Rev Genet. 2004 Apr;5(4):316-23 - PubMed
  116. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11039-41 - PubMed
  117. J Biol Chem. 2002 Jul 26;277(30):27567-74 - PubMed
  118. J Cell Biol. 2011 May 30;193(5):851-66 - PubMed
  119. J Biol Chem. 2002 May 10;277(19):16798-804 - PubMed
  120. Pharmacol Res. 2004 Oct;50(4):411-8 - PubMed
  121. Biochim Biophys Acta. 2007 Sep;1772(9):1093-102 - PubMed
  122. Mol Cell Biol. 1996 Nov;16(11):6229-41 - PubMed
  123. J Biol Chem. 2009 Mar 27;284(13):8495-506 - PubMed
  124. Mol Cell Biol. 1999 Jul;19(7):5179-88 - PubMed
  125. Neurobiol Aging. 2007 Jan;28(1):18.e1-4 - PubMed
  126. Neurochem Res. 2003 Oct;28(10):1553-61 - PubMed
  127. Brain Res Dev Brain Res. 1990 Oct 1;56(1):131-6 - PubMed
  128. Ann N Y Acad Sci. 2004 Dec;1030:339-47 - PubMed
  129. Neurobiol Aging. 2011 Sep;32(9):1725-9 - PubMed
  130. J Biol Chem. 2004 Jun 11;279(24):25374-80 - PubMed
  131. J Biol Chem. 2005 Sep 9;280(36):31537-47 - PubMed
  132. Nature. 1993 Mar 4;362(6415):75-9 - PubMed
  133. J Neurosci. 2003 Jul 30;23(17):6914-27 - PubMed
  134. Sci STKE. 2003 Mar 04;2003(172):RE4 - PubMed
  135. EMBO Rep. 2006 Jul;7(7):739-45 - PubMed
  136. Neurology. 2005 Aug 9;65(3):404-11 - PubMed
  137. Neurobiol Aging. 2001 Jul-Aug;22(4):517-28 - PubMed
  138. EMBO Rep. 2007 Feb;8(2):136-40 - PubMed
  139. J Biol Chem. 2010 Jul 16;285(29):22350-9 - PubMed
  140. J Neurochem. 2009 Aug;110(4):1129-34 - PubMed
  141. Neuron. 2003 Apr 10;38(1):9-12 - PubMed
  142. J Biol Chem. 1999 Oct 22;274(43):30764-9 - PubMed
  143. Curr Opin Genet Dev. 2000 Dec;10(6):668-74 - PubMed
  144. Biochem J. 1998 Jan 15;329 ( Pt 2):209-23 - PubMed

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