| MyD88 Deficiency Ameliorates β-Amyloidosis in an Animal Model of Alzheimer's Disease. | |
| | |
MedLine Citation:
|
PMID: 21763676 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The accumulation of β-amyloid protein (Aβ) in the brain is thought to be a primary etiologic event in Alzheimer's disease (AD). Fibrillar Aβ plaques, a hallmark of AD abnormality, are closely associated with activated microglia. Activated microglia have contradictory roles in the pathogenesis of AD, being either neuroprotective (by clearing harmful Aβ and repairing damaged tissues) or neurotoxic (by producing proinflammatory cytokines and reactive oxygen species). Aβ aggregates can activate microglia by interacting with multiple toll-like receptors (TLRs), the pattern-recognition receptors of the innate immune system. Because the adapter protein MyD88 is essential for the downstream signaling of all TLRs, except TLR3, we investigated the effects of MyD88 deficiency (MyD88(-/-)) on Aβ accumulation and microglial activation in an AD mouse model. MyD88 deficiency decreased Aβ load and microglial activation in the brain. The decrease in Aβ load in an MyD88(-/-) AD mouse model was associated with increased and decreased protein expression of apolipoprotein E (apoE) and CX3CR1, respectively, compared with that in an MyD88 wild-type AD mouse model. These results suggest that MyD88 deficiency may reduce Aβ load by enhancing the phagocytic capability of microglia through fractalkine (the ligand of CX3CR1) signaling and by promoting apoE-mediated clearance of Aβ from the brain. These findings also suggest that chronic inflammatory responses induced by Aβ accumulation via the MyD88-dependent signaling pathway exacerbate β-amyloidosis in AD. |
| | |
Authors:
|
Jeong-Eun Lim; Jinghong Kou; Min Song; Abhinandan Pattanayak; Jingji Jin; Robert Lalonde; Ken-Ichiro Fukuchi |
Related Documents
:
|
12106786 - The role of toll-like receptors in immunity against mycobacterial infection. 17929296 - Toll-like receptor-mediated control of hbv replication by nonparenchymal liver cells in... 20547386 - Double stranded rna- relative to other tlr ligand-activated dendritic cells induce extr... 16862146 - The endocytic pathway mediates cell entry of dsrna to induce rnai silencing. 19949076 - Mechanisms for glycolipid antigen-driven cytokine polarization by valpha14i nkt cells. 18340346 - The scf fsn-1 ubiquitin ligase controls germline apoptosis through cep-1/p53 in c. eleg... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-7-14 |
Journal Detail:
|
Title: The American journal of pathology Volume: - ISSN: 1525-2191 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
|
Created Date: 2011-7-18 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A Role for Vascular Deficiency in Retinal Pathology in a Mouse Model of Ataxia-Telangiectasia.
Next Document: Neutrophil Elastase Is Produced by Pulmonary Artery Smooth Muscle Cells and Is Linked to Neointimal ...