PMID- 33130223
OWN - NLM
STAT- MEDLINE
DCOM- 20211207
LR  - 20240330
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 148
DP  - 2021 Jan
TI  - 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.
PG  - 105150
LID - S0969-9961(20)30425-3 [pii]
LID - 10.1016/j.nbd.2020.105150 [doi]
AB  - 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.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Pentz, Rowan
AU  - Pentz R
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. 
      Electronic address: rowan.pentz@mail.mcgill.ca.
FAU - Iulita, M Florencia
AU  - Iulita MF
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; 
      Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant 
      Pau, Biomedical Research Institute Sant Pau, Universitat Autonoma de Barcelona, 
      Barcelona, Spain. Electronic address: florencia.iulita@gmail.com.
FAU - Mikutra-Cencora, Maya
AU  - Mikutra-Cencora M
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada. 
      Electronic address: maya.mikutra-cencora@umontreal.ca.
FAU - Ducatenzeiler, Adriana
AU  - Ducatenzeiler A
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada. 
      Electronic address: Adriana.ducatenzeiler@mcgill.ca.
FAU - Bennett, David A
AU  - Bennett DA
AD  - Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 
      USA. Electronic address: David_A_Bennett@rush.edu.
FAU - Cuello, A Claudio
AU  - Cuello AC
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, Canada; 
      Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; 
      Department of Anatomy and Cell Biology, McGill University, Montreal, Canada. 
      Electronic address: claudio.cuello@mcgill.ca.
LA  - eng
GR  - P30 AG010161/AG/NIA NIH HHS/United States
GR  - R01 AG015819/AG/NIA NIH HHS/United States
GR  - RF1 AG056850/AG/NIA NIH HHS/United States
GR  - 20129MOP-285643-PT-CFAA-22808/CIHR/Canada
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201030
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (RNA, Messenger)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Alzheimer Disease/*metabolism/pathology
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - Cerebral Cortex/*metabolism/pathology
MH  - Cognitive Dysfunction/metabolism/pathology
MH  - Female
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics/metabolism
MH  - Nerve Growth Factor/*metabolism
MH  - Proteolysis
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Transgenic
MH  - Sex Factors
PMC - PMC7856186
MID - NIHMS1650339
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Basal forebrain cholinergic neurons
OT  - Matrix metalloproteinase-3
OT  - NGF metabolic pathway
OT  - Nerve growth factor
OT  - proNGF
COIS- Conflict of interest The authors have no conflict of interest to report.
EDAT- 2020/11/02 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/02/03
CRDT- 2020/11/01 20:31
PHST- 2020/08/09 00:00 [received]
PHST- 2020/10/20 00:00 [revised]
PHST- 2020/10/23 00:00 [accepted]
PHST- 2020/11/02 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/11/01 20:31 [entrez]
PHST- 2021/02/03 00:00 [pmc-release]
AID - S0969-9961(20)30425-3 [pii]
AID - 10.1016/j.nbd.2020.105150 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2021 Jan;148:105150. doi: 10.1016/j.nbd.2020.105150. Epub 2020 Oct 
      30.