Apolipoprotein E and oxidative stress in brain with relevance to Alzheimer's disease.
Aldehydes
Alzheimer Disease
/ metabolism
Amyloid beta-Peptides
/ metabolism
Animals
Apolipoprotein E2
/ metabolism
Apolipoprotein E3
/ metabolism
Apolipoprotein E4
/ metabolism
Apolipoproteins E
/ metabolism
Brain
/ metabolism
Cell Death
Humans
Lipid Peroxidation
Mice
Neurons
/ metabolism
Oxidative Stress
Protein Isoforms
/ metabolism
Alzheimer's disease
Apolipoprotein E
Key cysteine residues
Oxidative stress
Targeted replacement mice
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
01
11
2019
revised:
26
01
2020
accepted:
06
02
2020
pubmed:
10
2
2020
medline:
31
3
2021
entrez:
10
2
2020
Statut:
ppublish
Résumé
Inheritance of apolipoprotein E4 (APOE4) is a major risk factor for development of Alzheimer's disease (AD). This lipoprotein, in contrast to apoE2, has arginine residues at positions 112 and 158 in place of cysteines in the latter isoform. In apoE3, the Cys at residue 158 is replaced by an arginine residue. This differential amino acid composition of the three genotypes of APOE have profound influence on the structure, binding properties, and multiple functions of this lipoprotein. Moreover, AD brain is under a high degree of oxidative stress, including that associated with amyloid β-peptide (Aβ) oligomers. Lipid peroxidation produces the highly reactive and neurotoxic molecule, 4-hydroxynonenal (HNE) that forms covalent bonds with cysteine residues (Cys) [as well as with Lys and His residues]. Covalently modified Cys significantly alter structure and function of modified proteins. HNE bound to Cys residue(s) on apoE2 and apoE3 lessens the chance of HNE damage other proteins. apoE4, lacking Cys residues, is unable to scavenge HNE, permitting this latter neurotoxic molecule to lead to oxidative modification of neuronal proteins and eventual cell death. We posit that this lack of HNE scavenging activity in apoE4 significantly contributes to the association of APOE4 inheritance and increased risk of developing AD. Apoe knock-out mice provide insights into the role of this lipoprotein in oxidative stress. Targeted replacement mice in which the mouse gene of Apoe is separately replaced by the human APOE2, APOE3, or APOE4 genes, while keeping the mouse promoter assures the correct location and amount of the human protein isoform. Human APOE targeted replacement mice have been used to investigate the notion that oxidative damage to and death of neurons in AD and its earlier stages is related to APOE genotype. This current paper reviews the intersection of human APOE genotype, oxidative stress, and diminished function of this lipoprotein as a major contributing risk factor for development of AD. Discussion of potential therapeutic strategies to mitigate against the elevated risk of developing AD with inheritance of the APOE4 allele also is presented.
Identifiants
pubmed: 32036033
pii: S0969-9961(20)30070-X
doi: 10.1016/j.nbd.2020.104795
pmc: PMC7085980
mid: NIHMS1566301
pii:
doi:
Substances chimiques
Aldehydes
0
Amyloid beta-Peptides
0
Apolipoprotein E2
0
Apolipoprotein E3
0
Apolipoprotein E4
0
Apolipoproteins E
0
Protein Isoforms
0
4-hydroxy-2-nonenal
K1CVM13F96
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
104795Subventions
Organisme : NIA NIH HHS
ID : R01 AG060056
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Neurobiol Dis. 2015 Dec;84:22-38
pubmed: 25926349
J Neurochem. 1997 Sep;69(3):1161-9
pubmed: 9282939
Neurology. 2005 Apr 12;64(7):1152-6
pubmed: 15824339
Neurology. 2019 Oct 22;93(17):e1647-e1659
pubmed: 31371569
Free Radic Res. 2011 Jan;45(1):59-72
pubmed: 20942567
Neurobiol Aging. 2002 Sep-Oct;23(5):777-85
pubmed: 12392781
Free Radic Biol Med. 1999 Sep;27(5-6):544-53
pubmed: 10490274
Neurobiol Dis. 2006 May;22(2):223-32
pubmed: 16466929
Free Radic Biol Med. 2007 Sep 1;43(5):658-77
pubmed: 17664130
J Alzheimers Dis. 2018;62(3):1319-1335
pubmed: 29562533
Free Radic Biol Med. 2016 Feb;91:1-9
pubmed: 26675344
Curr Pharm Des. 2015;21(1):114-20
pubmed: 25330331
J Alzheimers Dis. 2018;62(3):965-992
pubmed: 29562546
J Neuropathol Exp Neurol. 2000 Sep;59(9):751-8
pubmed: 11005255
J Neurochem. 2006 Jan;96(1):1-13
pubmed: 16305625
Biochemistry. 2001 Feb 27;40(8):2548-54
pubmed: 11327877
Redox Biol. 2019 May;23:101162
pubmed: 30876754
Free Radic Biol Med. 2018 Jan;114:94-101
pubmed: 28807816
J Alzheimers Dis. 2005 Apr;7(2):135-8; discussion 173-80
pubmed: 15851851
Brain Res. 2007 May 7;1148:243-8
pubmed: 17395167
J Neurochem. 2000 Apr;74(4):1579-86
pubmed: 10737615
Nature. 2017 Sep 28;549(7673):523-527
pubmed: 28959956
Lipids Health Dis. 2016 Jul 25;15:121
pubmed: 27457486
Brain Res. 2017 Apr 1;1660:27-35
pubmed: 28163090
Trends Mol Med. 2001 Dec;7(12):548-54
pubmed: 11733217
J Cell Mol Med. 2007 Nov-Dec;11(6):1227-38
pubmed: 18205697
Science. 1988 Apr 29;240(4852):622-30
pubmed: 3283935
J Alzheimers Dis. 2017;58(3):613-630
pubmed: 28527212
Brain Res Mol Brain Res. 2001 Jan 31;86(1-2):76-83
pubmed: 11165374
Free Radic Biol Med. 2014 Sep;74:157-74
pubmed: 24996204
J Alzheimers Dis. 2016;51(4):1265-74
pubmed: 26923023
Neurosci Lett. 2006 Apr 24;397(3):170-3
pubmed: 16413966
Neurobiol Aging. 2007 Dec;28(12):1853-62
pubmed: 17050040
Antioxid Redox Signal. 2017 Mar 10;26(8):364-387
pubmed: 27626216
J Neuropathol Exp Neurol. 2009 Jan;68(1):1-14
pubmed: 19104448
Nat Rev Neurol. 2019 Sep;15(9):501-518
pubmed: 31367008
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8098-102
pubmed: 8367470
Neurobiol Dis. 2000 Feb;7(1):23-37
pubmed: 10671320
Antioxid Redox Signal. 2012 Dec 1;17(11):1610-55
pubmed: 22115501
Brain Res. 2002 Jan 4;924(1):90-7
pubmed: 11743999
Ann Neurol. 2016 May;79(5):758-774
pubmed: 26933942
Neurobiol Aging. 2009 May;30(5):672-81
pubmed: 17920160
J Biol Chem. 1996 May 3;271(18):10602-6
pubmed: 8631862
J Cell Mol Med. 2001 Jul-Sep;5(3):254-66
pubmed: 12067484
Neurobiol Aging. 2019 Sep;81:9-21
pubmed: 31207469
Free Radic Biol Med. 2010 Dec 1;49(11):1798-803
pubmed: 20869432
Sci Rep. 2017 Aug 14;7(1):8009
pubmed: 28808293
J Neurochem. 1995 Nov;65(5):2146-56
pubmed: 7595501
Neurobiol Dis. 2008 Mar;29(3):456-64
pubmed: 18077176
Free Radic Biol Med. 2002 Jun 1;32(11):1071-5
pubmed: 12031891
Nat Neurosci. 2005 Jan;8(1):79-84
pubmed: 15608634
J Exp Med. 2019 Nov 4;216(11):2546-2561
pubmed: 31601677
J Alzheimers Dis. 2017;56(2):601-617
pubmed: 28035917
Clin Chem Lab Med. 2008;46(4):439-45
pubmed: 18298341
Mol Chem Neuropathol. 1996 May-Aug;28(1-3):41-8
pubmed: 8871940
Biomolecules. 2012 Mar 01;2(1):143-64
pubmed: 24970131
Free Radic Biol Med. 2002 Oct 15;33(8):1115-20
pubmed: 12374623
Life Sci. 1995;56(14):1151-71
pubmed: 7475893
Chem Rev. 2018 Feb 14;118(3):1338-1408
pubmed: 29400454
J Neuropathol Exp Neurol. 1996 Feb;55(2):202-10
pubmed: 8786379
Nat Rev Neurosci. 2019 Mar;20(3):148-160
pubmed: 30737462
Dis Markers. 2015;2015:746329
pubmed: 26696693
Neurochem Res. 2019 Jun;44(6):1297-1305
pubmed: 30225748
Biochem Biophys Res Commun. 1995 Mar 17;208(2):657-63
pubmed: 7695621
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18694-9
pubmed: 16344479
Free Radic Biol Med. 2014 Nov;76:89-95
pubmed: 25151119
J Neurochem. 2004 Aug;90(4):1011-8
pubmed: 15287908
Exp Gerontol. 2009 Oct;44(10):625-33
pubmed: 19622391
Neurobiol Aging. 2016 Jun;42:1-12
pubmed: 27143416
J Alzheimers Dis. 2014;41(1):43-60
pubmed: 24577472
Free Radic Biol Med. 2004 May 1;36(9):1155-62
pubmed: 15082069
Neurobiol Dis. 2010 Aug;39(2):221-8
pubmed: 20399861
J Neurochem. 2019 Nov;151(4):459-487
pubmed: 30216447
Prog Brain Res. 1998;118:269-80
pubmed: 9932448
Nat Rev Neurosci. 2000 Oct;1(1):51-8
pubmed: 11252768
Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):269-75
pubmed: 15650414
Free Radic Biol Med. 2018 Jan;114:102-109
pubmed: 28935420
Free Radic Biol Med. 1991;11(1):81-128
pubmed: 1937131
Free Radic Biol Med. 2013 Sep;62:157-169
pubmed: 23044265
Free Radic Biol Med. 2017 Oct;111:253-261
pubmed: 27789292
Sci Rep. 2016 Sep 02;6:32583
pubmed: 27585646
J Neurosci. 1995 Sep;15(9):6239-49
pubmed: 7666206
Clin Chem. 2005 Jun;51(6):944-51
pubmed: 15805147
Brain Pathol. 2016 Sep;26(5):632-47
pubmed: 27327899
Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5644-51
pubmed: 16567625
Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):284-9
pubmed: 14688411
J Neuropathol Exp Neurol. 2001 Aug;60(8):759-67
pubmed: 11487050
Comput Struct Biotechnol J. 2017 Jun 06;15:359-365
pubmed: 28660014
Lancet Neurol. 2018 Mar;17(3):241-250
pubmed: 29397305
J Alzheimers Dis. 2010;19(1):221-8
pubmed: 20061641
J Neurochem. 2000 Apr;74(4):1426-33
pubmed: 10737598
J Lipid Res. 1999 Mar;40(3):447-55
pubmed: 10064733
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8838-43
pubmed: 11447277