Neuronal low-density lipoprotein receptor-related protein 1 (LRP1) enhances the anti-apoptotic effect of intravenous immunoglobulin (IVIg) in ischemic stroke

Lok, Ker Zhing, Manzanero, Silvia and Arumugam, Thiruma V. (2016) Neuronal low-density lipoprotein receptor-related protein 1 (LRP1) enhances the anti-apoptotic effect of intravenous immunoglobulin (IVIg) in ischemic stroke. Brain Research, 1644 192-202. doi:10.1016/j.brainres.2016.05.023


Author Lok, Ker Zhing
Manzanero, Silvia
Arumugam, Thiruma V.
Title Neuronal low-density lipoprotein receptor-related protein 1 (LRP1) enhances the anti-apoptotic effect of intravenous immunoglobulin (IVIg) in ischemic stroke
Journal name Brain Research   Check publisher's open access policy
ISSN 1872-6240
0006-8993
Publication date 2016-08-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.brainres.2016.05.023
Open Access Status Not Open Access
Volume 1644
Start page 192
End page 202
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Collection year 2017
Language eng
Abstract The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional and multi-ligand endocytic receptor abundantly expressed in neurons. Intravenous immunoglobulin (IVIg) is a purified preparation of plasma-derived human immunoglobulin used for the treatment of several neurological inflammatory disorders, and proposed for the treatment of stroke for its potent neuroprotective effects. LRP1 has been shown to be involved in the transcytosis of IVIg, and IVIg-LRP1 interaction leads to LRP1 tyrosine phosphorylation, which may contribute to the anti-inflammatory effects of IVIg. However, the question remains whether IVIg could induce its neuroprotective effects via LRP1 in neurons under ischemic stroke conditions. In cultured neurons and in a transient ischemic mouse model, ischemia decrease LRP1 levels and phosphorylation, and IVIg blocks these effects. In ischemic neurons, LRP1 antagonism by receptor associated protein (RAP) enhances the activation of pro-death signaling pathways such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and caspase-3, and IVIg reduces these effects. When applied to ischemic neuronal cultures, RAP induces a dramatic drop in Akt activation, and IVIg reverses this effect, as it does with the decrease in Bcl-2 levels caused by ischemic injury in the presence of RAP. Altogether, these results show evidence of LRP1 expression and activity modulation by IVIg, and support the role of LRP1 as a partner of IVIg in the execution of its neuroprotective effects.
Keyword Apoptosis
Ischemia
IVIg
LRP1
MAPK
Neuroprotection
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
Australian Institute for Bioengineering and Nanotechnology Publications
 
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