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Participation of Glial Cells in the Pathogenesis of AD: A Different View on Neuroinflammation

  • Rommy von Bernhardi
Chapter

Abstract

Inflammation has been linked to Alzheimer's disease (AD). The accepted view is that inflammation is secondary to amyloid-β (Aβ) accumulation or neurodegeneration. However, I propose that glial dysfunction and the resulting imbalance between the cytotoxic inflammatory and neuroprotective-modulator activity could be the pathological mechanism behind AD. Such unbalance could be promoted by conditions like hypoxia and inflammation, which are frequently observed in aged individuals. A strong inflammatory response can promote defective processing of the amyloid-β protein precursor (AβPP) and the handling of Aβ by glial cells, resulting in the accumulation of Aβ and further inflammation. Proinflammatory conditions also enhance microglial cell activation by AβPP and Aβ and reduce astrocytes-mediated inhibition of microglial activation. These observations indicate that glial cell response to Aβ can be critically dependent on the priming of glial cells by proinflammatory factors. Astrocytes play a major role in the pathophysiology of AD, both promoting damage and mediating neuroprotection. Persistent inflammation can impair modulation and promote microglia-mediated neurotoxicity. Altogether, I propose that dysfunctional glia could result in both neuroinflammation and impaired neuronal function in AD.

Keywords

Nitric Oxide Glial Cell Microglial Cell Amyloid Plaque Glial Activation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

amyloid-β

AβPP

amyloid-β protein precursor

AD

Alzheimer's disease

BACE 1

β-secretase cleaving enzyme 1

CNS

central nervous system

COX

cyclooxygenase

COX-2

inducible form of cyclooxygenase

ERK

extracellular signal-regulated kinases

IFN-γ

interferon-γ

IL-1β

interleukin-1β

IL-6

interleukin-6

iNOS

inducible nitric oxide synthase

JNK

jun N-terminal kinase

LPS

lipopolysaccharide

LTP

long-term potentiation

MAPKs

mitogen-activated protein kinases

MCP-1

monocyte chemotactic protein-1

MHC-class II

major histocompatibility complex class II

MKP-1

MAPK phosphatase type 1

NF-κB

nuclear factor-κ B;

NGF

nerve growth factor

NO

nitric oxide

NSAIDs

nonsteroidal anti-inflammatory drugs

ROS

reactive oxygen species

SRs

scavenger receptors

STAT1

signal-transducer and activator of transcription-1

TGF-β

transforming growth factor-β

TNF-α

tumor necrosis factor-α

Notes

Acknowledgments

I thank Dr. Jaime Eugenín for his longstanding support and his critical reading of the manuscript. I gratefully acknowledge technical support of G. Ramírez and support by grant 1040831 from FONDECYT to RvB.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of NeurologyFaculty of Medicine, Pontificia Universidad Católica de ChileSantiago

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