Involvement of Matrix Metalloproteinase-9 in Amyloid-β 1-42-Induced Shedding of the Pericyte Proteoglycan NG2.
Research output: Contribution to journal › Article
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.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Journal of Neuropathology and Experimental Neurology|
|Publication status||Published - 2014|
Related research output
Nina Schultz, 2018, Lund: Lund University: Faculty of Medicine. 106 p.
Research output: Thesis › Doctoral Thesis (compilation)