title: Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging.
abstract: The roles of amyloid precursor protein (APP) family members in normal brain function are poorly understood. Under physiological conditions the majority of APP appears to be processed along the non-amyloidogenic pathway leading to the formation of the secreted N-terminal APP fragment sAPPα. This cleavage product of APP has been implicated in several physiological processes such as neuroprotection, synaptic plasticity, neurite outgrowth and synaptogenesis. In this review we focus on the role of APP family members in neuroprotection and summarize the cellular and molecular mechanisms which are believed to mediate this effect. We propose that a reduction of APP processing along the non-amyloidogenic pathway during brain aging could result in an enhanced susceptibility of neurons to cellular stress and could contribute to neurodegeneration in Alzheimer's disease.
authors.affiliation: Experimental Neurosurgery, Neuroscience Center, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. koegel@em.uni-frankfurt.de
authors.forename: Donat
authors.initials: D
authors.lastname: Kögel
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
authors.forename: Christian
authors.initials: C
authors.lastname: Behl
mesh_terms: D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D005810:Multigene Family / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents
references.citation: J Biol Chem. 2002 Aug 9;277(32):28530-6
references.pmid: 12032152
references.citation: Eur J Cell Biol. 2004 Dec;83(11-12):701-8
references.pmid: 15679114
references.citation: Neurobiol Aging. 2012 Sep;33(9):2200-9
references.pmid: 21803450
references.citation: Neurodegener Dis. 2006;3(4-5):239-46
references.pmid: 17047363
references.citation: Biochim Biophys Acta. 2009 Oct;1790(10):1124-32
references.pmid: 19632303
references.citation: J Biol Chem. 2003 Aug 15;278(33):31261-8
references.pmid: 12761223
references.citation: J Biol Chem. 2007 May 4;282(18):13833-44
references.pmid: 17314098
references.citation: J Neurochem. 1994 Aug;63(2):781-4
references.pmid: 8035204
references.citation: J Neurochem. 2004 Dec;91(6):1260-74
references.pmid: 15584903
references.citation: Nature. 1996 Jan 4;379(6560):74-8
references.pmid: 8538744
references.citation: Brain Res. 2011 Mar 10;1378:137-43
references.pmid: 21215734
references.citation: Eur J Neurosci. 2004 Oct;20(8):2071-8
references.pmid: 15450086
references.citation: Am J Pathol. 2000 Jul;157(1):277-86
references.pmid: 10880397
references.citation: J Neurosci. 2000 Nov 1;20(21):7951-63
references.pmid: 11050115
references.citation: Neurosci Lett. 1995 Sep 22;198(1):52-6
references.pmid: 8570096
references.citation: J Cell Sci. 2009 Oct 15;122(Pt 20):3703-14
references.pmid: 19773363
references.citation: J Biol Chem. 2002 Feb 1;277(5):3767-75
references.pmid: 11724784
references.citation: J Neurotrauma. 1998 Nov;15(11):993-1003
references.pmid: 9840772
references.citation: Neuroscience. 1998 Mar;83(2):429-38
references.pmid: 9460751
references.citation: FASEB J. 2003 Oct;17(13):1951-3
references.pmid: 12923068
references.citation: Cell Death Differ. 1998 Oct;5(10):858-66
references.pmid: 10203685
references.citation: J Neurosci. 2008 Jul 2;28(27):6926-37
references.pmid: 18596167
references.citation: Neuron. 2003 Jun 19;38(6):899-914
references.pmid: 12818176
references.citation: Curr Alzheimer Res. 2012 Feb;9(2):157-64
references.pmid: 21605036
references.citation: J Neurosci. 2010 Nov 10;30(45):14946-54
references.pmid: 21068297
references.citation: Cell. 1995 May 19;81(4):525-31
references.pmid: 7758106
references.citation: Chem Res Toxicol. 1997 May;10(5):507-17
references.pmid: 9168247
references.citation: Exp Neurol. 1999 Oct;159(2):441-50
references.pmid: 10506515
references.citation: Curr Alzheimer Res. 2007 Sep;4(4):412-7
references.pmid: 17908044
references.citation: J Neurosci. 1997 Dec 15;17(24):9407-14
references.pmid: 9390996
references.citation: Brain Res Mol Brain Res. 2002 Dec;108(1-2):102-20
references.pmid: 12480183
references.citation: Cell Death Differ. 2005 Jan;12(1):1-9
references.pmid: 15592359
references.citation: Biochem Biophys Res Commun. 1991 Nov 27;181(1):265-71
references.pmid: 1958195
references.citation: J Neurochem. 2003 Oct;87(1):248-56
references.pmid: 12969271
references.citation: Prog Neurobiol. 2008 Aug;85(4):393-406
references.pmid: 18603345
references.citation: Brain Res. 2006 Jun 13;1094(1):38-46
references.pmid: 16697978
references.citation: J Neurosci Res. 2001 Mar 1;63(5):410-20
references.pmid: 11223916
references.citation: J Biol Chem. 2003 Jun 20;278(25):22946-55
references.pmid: 12665528
references.citation: Neuron. 1993 Feb;10(2):243-54
references.pmid: 8094963
references.citation: Ann Neurol. 2009 Mar;65(3):294-303
references.pmid: 19334058
references.citation: J Biol Chem. 2002 Jun 7;277(23):20979-90
references.pmid: 11877414
references.citation: Autophagy. 2011 Jul;7(7):795-8
references.pmid: 21681022
references.citation: Neurosci Lett. 2009 Feb 20;451(2):119-23
references.pmid: 19073233
references.citation: EMBO J. 2009 Apr 8;28(7):889-901
references.pmid: 19229298
references.citation: Curr Drug Targets CNS Neurol Disord. 2002 Feb;1(1):31-49
references.pmid: 12769633
references.citation: Exp Neurol. 1994 Jul;128(1):1-12
references.pmid: 8070512
references.citation: J Neurosci. 2001 Sep 1;21(17):6597-607
references.pmid: 11517249
references.citation: J Biol Chem. 2003 Feb 7;278(6):3897-902
references.pmid: 12458207
references.citation: Neurosci Lett. 2008 Oct 24;444(2):127-31
references.pmid: 18722509
references.citation: J Neurosci. 2005 Dec 14;25(50):11542-52
references.pmid: 16354912
references.citation: Mol Neurodegener. 2006 Jul 03;1:5
references.pmid: 16930452
references.citation: Cell. 1994 Dec 2;79(5):755-65
references.pmid: 8001115
references.citation: Cell Mol Life Sci. 2009 Jul;66(14):2299-318
references.pmid: 19333550
references.citation: J Biol Chem. 2006 Feb 3;281(5):2405-13
references.pmid: 16303768
references.citation: J Cell Sci. 2007 Sep 15;120(Pt 18):3157-61
references.pmid: 17878232
references.citation: J Biol Chem. 1998 May 15;273(20):12341-51
references.pmid: 9575187
references.citation: Exp Neurol. 2002 Jun;175(2):407-14
references.pmid: 12061870
references.citation: Exp Neurol. 1994 Sep;129(1):112-9
references.pmid: 7925833
references.citation: Brain Res. 1993 Dec 3;629(2):275-82
references.pmid: 7906601
references.citation: Nature. 2009 Feb 19;457(7232):981-9
references.pmid: 19225519
references.citation: Eur J Cell Biol. 2012 Apr;91(4):234-9
references.pmid: 21459473
references.citation: J Neurosci. 2004 Sep 1;24(35):7707-17
references.pmid: 15342738
references.citation: EMBO J. 2004 Oct 13;23(20):4106-15
references.pmid: 15385965
references.citation: Brain Res. 2001 Jul 13;907(1-2):222-32
references.pmid: 11430905
references.citation: J Biol Chem. 2011 May 27;286(21):18414-25
references.pmid: 21460223
references.citation: Perspect Dev Neurobiol. 1998;5(4):337-52
references.pmid: 10533524
references.citation: Physiol Rev. 1997 Oct;77(4):1081-132
references.pmid: 9354812
references.citation: J Cell Biol. 2003 Jan 6;160(1):113-23
references.pmid: 12515826
references.citation: J Neurosci. 2007 Jul 18;27(29):7817-26
references.pmid: 17634375
references.citation: Biochem Soc Trans. 2007 Apr;35(Pt 2):416-20
references.pmid: 17371289
references.citation: Neurodegener Dis. 2006;3(3):134-47
references.pmid: 16954700
references.citation: Dev Biol. 1994 Feb;161(2):597-603
references.pmid: 8314003
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6158-62
references.pmid: 8650236
references.citation: Nat Rev Neurosci. 2002 Nov;3(11):862-72
references.pmid: 12415294
references.citation: Ann N Y Acad Sci. 2006 Dec;1090:455-65
references.pmid: 17384289
references.citation: Ann N Y Acad Sci. 1996 Jan 17;777:82-8
references.pmid: 8624131
references.citation: EMBO J. 2005 Aug 17;24(16):2944-55
references.pmid: 16052209
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7547-52
references.pmid: 10377452
references.citation: Nat Cell Biol. 2004 Nov;6(11):1054-61
references.pmid: 15516999
references.citation: J Biol Chem. 2002 Jul 26;277(30):27567-74
references.pmid: 12023290
references.citation: Biochim Biophys Acta. 2011 Jan;1808(1):236-43
references.pmid: 21036142
references.citation: Mol Cell Neurosci. 2007 May;35(1):57-63
references.pmid: 17383198
references.citation: Neural Dev. 2008 Jun 23;3:15
references.pmid: 18573216
references.citation: EMBO J. 2005 Oct 19;24(20):3624-34
references.pmid: 16193067
references.citation: Neuroscience. 1997 May;78(1):135-46
references.pmid: 9135095
references.citation: Biochem Biophys Res Commun. 2006 Dec 8;351(1):57-63
references.pmid: 17054906
references.citation: Cell. 2009 Jun 12;137(6):997-1000
references.pmid: 19524503
references.citation: J Neurosci. 2009 Sep 2;29(35):10788-801
references.pmid: 19726636
references.citation: PLoS One. 2011;6(6):e21337
references.pmid: 21695060
references.citation: J Biol Chem. 2007 Apr 6;282(14):10203-9
references.pmid: 17301053
references.citation: J Biol Chem. 2008 Oct 31;283(44):29615-9
references.pmid: 18650430
references.citation: Mol Cell Neurosci. 2010 Aug;44(4):386-93
references.pmid: 20472066
references.citation: Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5191-3
references.pmid: 8506366
references.citation: Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7450-4
references.pmid: 8052602
references.citation: J Biol Chem. 2009 May 29;284(22):15016-25
references.pmid: 19336403
references.citation: Neurology. 1990 Jul;40(7):1028-34
references.pmid: 2113204
references.citation: J Biol Chem. 2010 Dec 31;285(53):41443-54
references.pmid: 20961856
references.citation: Prog Neurobiol. 2003 May;70(1):1-32
references.pmid: 12927332