For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
30
views
33
references
 Top references
cited by
16
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      480
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      RIG-1 receptor expression in the pathology of Alzheimer’s disease

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Neuroinflammation plays a critical role in the pathogenesis of Alzheimer’s disease (AD) and involves activation of the innate immune response via recognition of diverse stimuli by pattern recognition receptors (PRRs). The inflammatory inducers and precise innate signaling pathway contributing to AD pathology remain largely undefined.

          Results

          In the present study we analyzed expression levels of innate immune proteins in temporal and occipital cortices from preclinical (no cognitive impairment, NCI, N = 22) to mild cognitive impairment (MCI, N = 20) associated with AD pathology (N = 20) and AD patients (N = 23). We found that retinoic acid-inducible gene-I (RIG-1) is significantly elevated in the temporal cortex and plasma in patients with MCI. In addition, primary human astrocytes stimulated with the RIG-1 ligand 5′ppp RNA showed increased expression of amyloid precursor protein (APP) and amyloid-β (Aβ), supporting the idea that RIG-1 is involved in the pathology of MCI associated with early progression to AD.

          Conclusion

          These findings suggest that RIG-1 may play a critical role in incipient AD.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          Alzheimer disease in the US population: prevalence estimates using the 2000 census.

          Liesi Hebert, Paul Scherr, Julia L Bienias … (2003)
          Current and future estimates of Alzheimer disease (AD) are essential for public health planning. To provide prevalence estimates of AD for the US population from 2000 through 2050. Alzheimer disease incidence estimates from a population-based, biracial, urban study, using a stratified random sampling design, were converted to prevalence estimates and applied to US Census Bureau estimates of US population growth. A geographically defined community of 3 adjacent neighborhoods in Chicago, Ill, applied to the US population. Alzheimer disease incidence was measured in 3838 persons free of AD at baseline; 835 persons were evaluated for disease incidence. Main Outcome Measure Current and future estimates of prevalence of clinically diagnosed AD in the US population. In 2000, there were 4.5 million persons with AD in the US population. By 2050, this number will increase by almost 3-fold, to 13.2 million. Owing to the rapid growth of the oldest age groups of the US population, the number who are 85 years and older will more than quadruple to 8.0 million. The number who are 75 to 84 years old will double to 4.8 million, while the number who are 65 to 74 years old will remain fairly constant at 0.3 to 0.5 million. The number of persons with AD in the US population will continue to increase unless new discoveries facilitate prevention of the disease.
          Article 0 comments Cited 358 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling.

            Michal Caspi Tal, Miwa Sasai, Heung Lee … (2009)
            Autophagy is a highly conserved process that maintains homeostasis by clearing damaged organelles and long-lived proteins. The consequences of deficiency in autophagy manifest in a variety of pathological states including neurodegenerative diseases, inflammatory disorders, and cancer. Here, we studied the role of autophagy in the homeostatic regulation of innate antiviral defense. Single-stranded RNA viruses are recognized by the members of the RIG-I-like receptors (RLRs) in the cytosol. RLRs signal through IPS-1, resulting in the production of the key antiviral cytokines, type I IFNs. Autophagy-defective Atg5(-/-) cells exhibited enhanced RLR signaling, increased IFN secretion, and resistance to infection by vesicular stomatitis virus. In the absence of autophagy, cells accumulated dysfunctional mitochondria, as well as mitochondria-associated IPS-1. Reactive oxygen species (ROS) associated with the dysfunctional mitochondria were largely responsible for the enhanced RLR signaling in Atg5(-/-) cells, as antioxidant treatment blocked the excess RLR signaling. In addition, autophagy-independent increase in mitochondrial ROS by treatment of cells with rotenone was sufficient to amplify RLR signaling in WT cells. These data indicate that autophagy contributes to homeostatic regulation of innate antiviral defense through the clearance of dysfunctional mitochondria, and revealed that ROS associated with mitochondria play a key role in potentiating RLR signaling.
            Article 0 comments Cited 213 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              TLR2 is a primary receptor for Alzheimer's amyloid β peptide to trigger neuroinflammatory activation.

              Botond Penke, Jochen Walter, Klaus Fassbender … (2012)
              Microglia activated by extracellularly deposited amyloid β peptide (Aβ) act as a two-edged sword in Alzheimer's disease pathogenesis: on the one hand, they damage neurons by releasing neurotoxic proinflammatory mediators (M1 activation); on the other hand, they protect neurons by triggering anti-inflammatory/neurotrophic M2 activation and by clearing Aβ via phagocytosis. TLRs are associated with Aβ-induced microglial inflammatory activation and Aβ internalization, but the mechanisms remain unclear. In this study, we used real-time surface plasmon resonance spectroscopy and conventional biochemical pull-down assays to demonstrate a direct interaction between TLR2 and the aggregated 42-aa form of human Aβ (Aβ42). TLR2 deficiency reduced Aβ42-triggered inflammatory activation but enhanced Aβ phagocytosis in cultured microglia and macrophages. By expressing TLR2 in HEK293 cells that do not endogenously express TLR2, we observed that TLR2 expression enabled HEK293 cells to respond to Aβ42. Through site-directed mutagenesis of tlr2 gene, we identified the amino acids EKKA (741-744) as a critical cytoplasmic domain for transduction of inflammatory signals. By coexpressing TLR1 or TLR6 in TLR2-transgenic HEK293 cells or silencing tlrs genes in RAW264.7 macrophages, we observed that TLR2-mediated Aβ42-triggered inflammatory activation was enhanced by TLR1 and suppressed by TLR6. Using bone marrow chimeric Alzheimer's amyloid precursor transgenic mice, we observed that TLR2 deficiency in microglia shifts M1- to M2-inflammatory activation in vivo, which was associated with improved neuronal function. Our study demonstrated that TLR2 is a primary receptor for Aβ to trigger neuroinflammatory activation and suggested that inhibition of TLR2 in microglia could be beneficial in Alzheimer's disease pathogenesis.
              Article 0 comments Cited 175 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Juan Pablo de Rivero Vaccari
                Frank J Brand III
                Christina Sedaghat
                Deborah C Mash
                W Dalton Dietrich
                Robert W Keane
                Journal
                Journal ID (nlm-ta): J Neuroinflammation
                Journal ID (iso-abbrev): J Neuroinflammation
                Title: Journal of Neuroinflammation
                Publisher: BioMed Central
                ISSN (Electronic): 1742-2094
                Publication date Collection: 2014
                Publication date (Electronic): 2 April 2014
                Volume: 11
                Page: 67
                Affiliations
                [1 ]Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
                [2 ]Department of Physiology & Biophysics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
                [3 ]Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
                [4 ]Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
                [5 ]The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA
                Article
                Publisher ID: 1742-2094-11-67
                DOI: 10.1186/1742-2094-11-67
                PMC ID: 3977677
                PubMed ID: 24694234
                SO-VID: abbb5c96-da7d-496c-b705-3ad0ffc7355e
                Copyright © Copyright © 2014 de Rivero Vaccari et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 9 December 2013
                Date accepted : 25 March 2014
                Categories
                Subject: Research

                ScienceOpen disciplines: Neurosciences
                Keywords: innate immunity,rig signaling,rlr,inflammation,alzheimer’s disease,mild cognitive impairment
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: innate immunity, rig signaling, rlr, inflammation, alzheimer’s disease, mild cognitive impairment

                Comments

                Comment on this article

                scite_

                Similar content480

                See all similar

                Cited by16

                See all cited by

                Most referenced authors877

                See all reference authors