Journal ArticleDOI
Expression of α2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP) in rat microglial cells
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TLDR
The first analysis of LRP expression and regulation in microglia is provided, opening the possibility that microglial cells could be related to the participation of L RP and its ligands in different pathophysiological states in brain.Abstract:
Low density lipoprotein receptor-related protein (LRP) participates in the uptake and degradation of several ligands implicated in neuronal pathophysiology including apolipoprotein E (apoE), activated a2 -macroglobulin (a2M*) and b-amyloid precursor protein (APP). The receptor is expressed in a variety of tissues. In the brain LRP is present in pyramidal-type neurons in cortical and hippocampal regions and in astrocytes that are activated as a result of injury or neoplasmic transformation. As LRP is expressed in the monocyte/macrophage cell system, we were interested in examining whether LRP is expressed in microglia. We isolated glial cells from the brain of neonatal rats and LRP was immunodetected both in microglial cells and in astrocytes expressing glial fibrillar acidic protein (GFAP). Microglial cells were able to bind and internalize LRP-specific ligand, a2M*. The internalization was inhibitable by RAP, with a Kd of 1.7 nM. The expression of LRP was upregulated by dexamethasone, and down-regulated by lipopolysaccharide (LPS), gamma interferon (IFN-g )o r ac ombination of both. LRP was less sensitive to dexamethasone in activated astrocytes than in microglia. We provided the first analysis of LRP expression and regulation in microglia. Our results open the possibility that microglial cells could be related to the participation of LRP and its ligands in different pathophysiological states in brain. J. Neurosci. Res. 60:401‐411, 2000. © 2000 Wiley-Liss, Inc.read more
Citations
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Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury.
Michael Costigan,Katia Befort,Laurie A. Karchewski,Robert S. Griffin,Donatella D'urso,Andrew Allchorne,Joanne Sitarski,James W Mannion,Richard E. Pratt,Clifford J. Woolf +9 more
TL;DR: The results support use of a P < 0.05 significance threshold for detecting regulated genes, despite the large number of hypothesis tests required, and identify parameters for microarray analysis which reduce error while identifying many putatively regulated genes.
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The role of microglia in amyloid clearance from the AD brain.
TL;DR: The mechanisms that microglia utilize to clear Aβ and the effectors that modulate the processes are explored.
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Phagocytosis of Microglia in the Central Nervous System Diseases
TL;DR: This review focuses on phagocytic phenotype of microglia in neurological diseases such as Alzheimer's disease, multiple sclerosis, Parkinson’s disease, traumatic brain injury, ischemic and other brain diseases.
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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease.
TL;DR: This work discusses glial dysfunction in AD with emphasis on neuronal and glial receptors that mediate Aβ-induced toxicity, and discusses other critical factors that may affect AD pathogenesis, including genetics, aging, variables related to environment, lifestyle habits, and APOE.
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Modulation of amyloid β-protein clearance and Alzheimer’s disease susceptibility by the LDL receptor–related protein pathway
David E. Kang,Claus U. Pietrzik,Larry Baum,Nathalie Chevallier,David E. Merriam,Maria Z. Kounnas,Steven L. Wagner,Juan C. Troncoso,Claudia H. Kawas,Robert Katzman,Edward H. Koo +10 more
TL;DR: This work provides the first in vivo evidence that the LRP pathway may modulate Abeta deposition and AD susceptibility by regulating the removal of soluble Abeta.
References
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Apolipoprotein e polymorphism and alzheimer's disease
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