Involvement of Matrix Metalloproteinase-9 in Amyloid-β 1-42-Induced Shedding of the Pericyte Proteoglycan NG2.
(2014) In Journal of Neuropathology and Experimental Neurology 73(7). p.684-692- Abstract
- Deposition of amyloid-β (Aβ) 1-42, the major component of senile plaques characteristic of Alzheimer disease, affects brain microvascular integrity and causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte degeneration. To understand the cellular events underlying Aβ1-42 effects on microvascular alterations, we investigated whether different aggregation forms of Aβ1-42 affect shedding of the pericyte proteoglycan NG2 and whether they affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in pericyte culture supernatants in response to fibril-enriched preparations of Aβ1-42. Conversely, oligomer-enriched preparations of Aβ1-42... (More)
- Deposition of amyloid-β (Aβ) 1-42, the major component of senile plaques characteristic of Alzheimer disease, affects brain microvascular integrity and causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte degeneration. To understand the cellular events underlying Aβ1-42 effects on microvascular alterations, we investigated whether different aggregation forms of Aβ1-42 affect shedding of the pericyte proteoglycan NG2 and whether they affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in pericyte culture supernatants in response to fibril-enriched preparations of Aβ1-42. Conversely, oligomer-enriched preparations of Aβ1-42 increased soluble NG2 levels in the supernatants. This increase was ablated by the MMP-9/MMP-2 inhibitor SB-3CT. There was also a trend toward increased MMP-9 activity observed after oligomeric Aβ1-42 exposure. Our results, demonstrating an Aβ1-42 aggregation-dependent effect on levels of NG2 and MMP-9, support previous studies showing an impact of Aβ1-42 on vascular integrity and thereby add to our understanding of mechanisms behind the microvascular changes commonly found in patients with Alzheimer disease. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4528798
- author
- Schultz, Nina LU ; Nielsen, Henrietta LU ; Minthon, Lennart LU and Wennström, Malin LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Neuropathology and Experimental Neurology
- volume
- 73
- issue
- 7
- pages
- 684 - 692
- publisher
- American Association of Neuropathologists
- external identifiers
-
- pmid:24918635
- wos:000338133900004
- scopus:84903314983
- ISSN
- 1554-6578
- DOI
- 10.1097/NEN.0000000000000084
- language
- English
- LU publication?
- yes
- id
- 7060b2a1-fc7e-4b63-9663-e46cc983cabb (old id 4528798)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24918635?dopt=Abstract
- date added to LUP
- 2016-04-01 09:55:13
- date last changed
- 2022-03-27 01:58:49
@article{7060b2a1-fc7e-4b63-9663-e46cc983cabb,
abstract = {{Deposition of amyloid-β (Aβ) 1-42, the major component of senile plaques characteristic of Alzheimer disease, affects brain microvascular integrity and causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte degeneration. To understand the cellular events underlying Aβ1-42 effects on microvascular alterations, we investigated whether different aggregation forms of Aβ1-42 affect shedding of the pericyte proteoglycan NG2 and whether they affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in pericyte culture supernatants in response to fibril-enriched preparations of Aβ1-42. Conversely, oligomer-enriched preparations of Aβ1-42 increased soluble NG2 levels in the supernatants. This increase was ablated by the MMP-9/MMP-2 inhibitor SB-3CT. There was also a trend toward increased MMP-9 activity observed after oligomeric Aβ1-42 exposure. Our results, demonstrating an Aβ1-42 aggregation-dependent effect on levels of NG2 and MMP-9, support previous studies showing an impact of Aβ1-42 on vascular integrity and thereby add to our understanding of mechanisms behind the microvascular changes commonly found in patients with Alzheimer disease.}},
author = {{Schultz, Nina and Nielsen, Henrietta and Minthon, Lennart and Wennström, Malin}},
issn = {{1554-6578}},
language = {{eng}},
number = {{7}},
pages = {{684--692}},
publisher = {{American Association of Neuropathologists}},
series = {{Journal of Neuropathology and Experimental Neurology}},
title = {{Involvement of Matrix Metalloproteinase-9 in Amyloid-β 1-42-Induced Shedding of the Pericyte Proteoglycan NG2.}},
url = {{http://dx.doi.org/10.1097/NEN.0000000000000084}},
doi = {{10.1097/NEN.0000000000000084}},
volume = {{73}},
year = {{2014}},
}