A new role for matrix metalloproteinase-3 in the NGF metabolic pathway: Proteolysis of mature NGF and sex-specific differences in the continuum of Alzheimer's pathology.
Alzheimer's disease
Basal forebrain cholinergic neurons
Matrix metalloproteinase-3
NGF metabolic pathway
Nerve growth factor
proNGF
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
09
08
2020
revised:
20
10
2020
accepted:
23
10
2020
pubmed:
2
11
2020
medline:
15
12
2021
entrez:
1
11
2020
Statut:
ppublish
Résumé
Matrix metalloproteinase-3 (MMP-3) has been associated with risk of Alzheimer's disease (AD). In this study we introduce a novel role for MMP-3 in degrading nerve growth factor (NGF) in vivo and examine its mRNA and protein expression across the continuum of AD pathology. We provide evidence that MMP-3 participates in the degradation of mature NGF in vitro and in vivo and that it is secreted from the rat cerebral cortex in an activity-dependent manner. We show that cortical MMP-3 is upregulated in the McGill-R-Thy1-APP transgenic rat model of AD-like amyloidosis. A similar upregulation was found in AD and MCI brains as well as in cognitively normal individuals with elevated amyloid deposition. We also observed that frontal cortex MMP-3 protein levels are higher in males. MMP-3 protein correlated with more AD neuropathology, markers of NGF metabolism, and lower cognitive scores in males but not in females. These results suggest that MMP-3 upregulation in AD might contribute to NGF dysmetabolism, and therefore to cholinergic atrophy and cognitive deficits, in a sex-specific manner. MMP-3 should be further investigated as a biomarker candidate or as a therapeutic target in AD.
Identifiants
pubmed: 33130223
pii: S0969-9961(20)30425-3
doi: 10.1016/j.nbd.2020.105150
pmc: PMC7856186
mid: NIHMS1650339
pii:
doi:
Substances chimiques
RNA, Messenger
0
Nerve Growth Factor
9061-61-4
Matrix Metalloproteinase 3
EC 3.4.24.17
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105150Subventions
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG056850
Pays : United States
Organisme : CIHR
ID : 20129MOP-285643-PT-CFAA-22808
Pays : Canada
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Pharmacol Res. 2019 Mar;141:249-263
pubmed: 30611853
J Neurochem. 2008 Jul;106(1):405-15
pubmed: 18397366
Free Radic Biol Med. 2005 Jul 1;39(1):71-80
pubmed: 15925279
Biochem Biophys Res Commun. 2004 Mar 26;316(1):182-8
pubmed: 15003528
Neurosci Lett. 2009 Dec 11;466(3):135-8
pubmed: 19786072
Nat Rev Neurol. 2018 Aug;14(8):457-469
pubmed: 29985474
Eur J Neurol. 2020 Jun;27(6):928-943
pubmed: 32056347
Curr Alzheimer Res. 2016;13(7):800-8
pubmed: 26825093
J Alzheimers Dis. 2010;20(1):113-26
pubmed: 20164597
J Neurotrauma. 2006 Dec;23(12):1750-65
pubmed: 17184186
J Endod. 2009 Apr;35(4):529-36
pubmed: 19345799
Acta Neuropathol. 2000 Feb;99(2):91-5
pubmed: 10672313
Curr Alzheimer Res. 2012 Jul;9(6):628-45
pubmed: 22471860
Mol Neurobiol. 2017 Jan;54(1):804-816
pubmed: 27351676
Glia. 2013 Jun;61(6):972-84
pubmed: 23554135
Neurosci Lett. 2015 May 19;595:116-21
pubmed: 25864780
Neurobiol Aging. 2008 Jun;29(6):874-81
pubmed: 17316907
Brain. 2014 Mar;137(Pt 3):860-72
pubmed: 24519975
J Neurosci. 2005 Apr 6;25(14):3701-11
pubmed: 15814801
J Immunol. 1998 Oct 1;161(7):3340-6
pubmed: 9759850
Eur J Neurosci. 2015 May;41(9):1245-62
pubmed: 25808554
Int Psychogeriatr. 2010 Sep;22(6):966-72
pubmed: 20561382
Science. 1982 Mar 5;215(4537):1237-9
pubmed: 7058341
J Neurosci. 1986 Aug;6(8):2155-62
pubmed: 3746405
Brain Res. 1983 Dec 19;289(1-2):375-9
pubmed: 6362777
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6735-40
pubmed: 16618925
Neurobiol Dis. 2006 Jul;23(1):87-96
pubmed: 16624562
Alzheimers Res Ther. 2010 Jun 24;2(3):20
pubmed: 20576109
J Physiol Paris. 1998 Jun-Aug;92(3-4):205-8
pubmed: 9789809
FASEB J. 2007 Jan;21(1):179-87
pubmed: 17116747
Stroke. 2001 May;32(5):1162-8
pubmed: 11340226
Structure. 2019 Jan 2;27(1):78-89.e3
pubmed: 30393051
J Neurosci. 2015 Sep 16;35(37):12766-78
pubmed: 26377465
Neuropsychopharmacology. 2011 Jan;36(1):52-73
pubmed: 20668433
J Neuropathol Exp Neurol. 2009 Aug;68(8):857-69
pubmed: 19606067
J Alzheimers Dis. 2014;40(3):667-78
pubmed: 24531161
J Immunol. 2010 Jul 1;185(1):615-23
pubmed: 20511551
Neurobiol Aging. 2014 Mar;35(3):614-22
pubmed: 24094581
J Mol Neurosci. 2010 Jan;40(1-2):230-5
pubmed: 19680822
J Biol Chem. 2010 May 28;285(22):16444-52
pubmed: 20368330
J Rheumatol. 2011 Aug;38(8):1644-50
pubmed: 21632677
J Invest Dermatol. 1995 Mar;104(3):384-90
pubmed: 7861007
Arch Neurol. 1974 Feb;30(2):113-21
pubmed: 4359364
Alzheimers Dement. 2016 Nov;12(11):1132-1148
pubmed: 27452424
J Cereb Blood Flow Metab. 2001 Dec;21(12):1393-400
pubmed: 11740200
Cereb Cortex. 2019 Jan 1;29(1):283-304
pubmed: 29228131
Neurobiol Dis. 2017 Dec;108:307-323
pubmed: 28865749
Neurosci Lett. 2004 Sep 9;367(3):336-9
pubmed: 15337261
J Biol Chem. 2006 Jun 30;281(26):17670-80
pubmed: 16648635
Learn Mem. 2004 Jan-Feb;11(1):43-9
pubmed: 14747516
Science. 1982 Jul 30;217(4558):408-14
pubmed: 7046051
Cereb Cortex. 2007 Jul;17(7):1712-21
pubmed: 17021275
Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2639-43
pubmed: 1557368
J Rheumatol. 1987 May;14 Spec No:41-2
pubmed: 3305938
J Neurosci. 2017 Feb 1;37(5):1240-1256
pubmed: 28069922
Clin Rheumatol. 2014 Feb;33(2):237-41
pubmed: 23917391
J Neurochem. 1996 Apr;66(4):1641-7
pubmed: 8627321
J Biol Chem. 1992 Feb 25;267(6):3581-4
pubmed: 1371271
Neurology. 1984 Jul;34(7):939-44
pubmed: 6610841
Neurology. 2006 Jun 27;66(12):1837-44
pubmed: 16801647
Nat Rev Neurol. 2019 Mar;15(3):135-147
pubmed: 30733618
Trends Pharmacol Sci. 2014 Jul;35(7):338-48
pubmed: 24962069
J Biol Chem. 2002 Apr 19;277(16):13589-96
pubmed: 11830584
Neurochem Res. 2006 Aug;31(8):1045-54
pubmed: 16871440
Am J Pathol. 2014 Sep;184(9):2560-72
pubmed: 25063530
Front Neurosci. 2019 Feb 12;13:62
pubmed: 30809111
Adv Exp Med Biol. 2016;949:311-332
pubmed: 27714696
Mol Cell Neurosci. 2001 Aug;18(2):210-20
pubmed: 11520181
Biochem Biophys Res Commun. 2013 Jan 4;430(1):419-24
pubmed: 23206705
Arch Oral Biol. 2011 May;56(5):413-20
pubmed: 21371688
J Neurochem. 2006 Mar;96(5):1227-41
pubmed: 16464240
Annu Rev Psychol. 1997;48:649-84
pubmed: 9046571
Immunol Today. 1994 Mar;15(3):103-7
pubmed: 8172641
Exp Neurol. 2009 Mar;216(1):122-31
pubmed: 19111539
Curr Alzheimer Res. 2018;15(11):1077-1084
pubmed: 29895246
Acta Neuropathol Commun. 2014 Jun 05;2:61
pubmed: 24903713
J Neurochem. 2008 Jul;106(2):770-80
pubmed: 18419763
Neuropathol Appl Neurobiol. 2008 Apr;34(2):205-15
pubmed: 17971072
Neurobiol Aging. 2007 Aug;28(8):1215-20
pubmed: 16822591
Matrix Biol. 2016 Jan;49:37-60
pubmed: 26407638
J Alzheimers Dis. 2019;67(1):327-341
pubmed: 30636741
J Neuropathol Exp Neurol. 2009 Dec;68(12):1309-18
pubmed: 19915485
Mol Psychiatry. 2020 Jun 2;:
pubmed: 32488129
Exp Neurol. 2012 Oct;237(2):470-6
pubmed: 22890115
J Biol Chem. 2017 Oct 6;292(40):16665-16676
pubmed: 28798232
Arthritis Rheum. 2000 Apr;43(4):852-8
pubmed: 10765930
Pain. 2020 Jul;161(7):1483-1496
pubmed: 32068663
Ann Rheum Dis. 2002 Feb;61(2):161-6
pubmed: 11796404
Prog Brain Res. 1993;98:265-77
pubmed: 8248516