Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease

Sasaki, Nobuyuki; Toki, Sadamu; Chowei, Hiroshi; Saito, Toshikazu; Nakano, Norihito; Hayashi, Yorihide; Takeuchi, Masayoshi; Makita, Zenji

doi:10.1016/s0006-8993(00)03075-4

Cited by 242 publications

(151 citation statements)

References 24 publications

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“…In clear contrast, AD samples exhibited a marked increase in immunoreactivity as well as in the molecular heterogeneity of the immunoreactive forms. These may belong to full-length RAGE (55 kDa) and to N-terminal RAGE (35 kDa), already identified in human brain tissue (35). The pathophysiological relevance of these findings is unknown but it is proposed that RAGE overexpression may reflect different responses to increased AGE or A␤ concentrations.…”

Section: Discussionmentioning

confidence: 94%

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

Pamplona

Dalfó

Ayala

et al. 2005

Journal of Biological Chemistry

257

242

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Diverse oxidative pathways, such as direct oxidation of amino acids, glycoxidation, and lipoxidation could contribute to Alzheimer disease pathogenesis. A global survey for the amount of structurally characterized probes for these reactions is lacking and could overcome the lack of specificity derived from measurement of 2,4-dinitrophenylhydrazine reactive carbonyls. Consequently we analyzed (i) the presence and concentrations of glutamic and aminoadipic semialdehydes, N ⑀ -(carboxymethyl)-lysine, N ⑀ -(carboxyethyl)-lysine, and N ⑀ -(malondialdehyde)-lysine by means of gas chromatography/mass spectrometry, (ii) the biological response through expression of the receptor for advanced glycation end products, (iii) the fatty acid composition in brain samples from Alzheimer disease patients and agematched controls, and (iv) the targets of N ⑀ -(malondialdehyde)-lysine formation in brain cortex by proteomic techniques. Alzheimer disease was associated with significant, although heterogeneous, increases in the concentrations of all evaluated markers. Alzheimer disease samples presented increases in expression of the receptor for advanced glycation end products with high molecular heterogeneity. Samples from Alzheimer disease patients also showed content of docosahexaenoic acid, which increased lipid peroxidizability. In accordance, N ⑀ -(malondialdehyde)-lysine formation targeted important proteins for both glial and neuronal homeostasis such as neurofilament L, ␣-tubulin, glial fibrillary acidic protein, ubiquinol-cytochrome c reductase complex protein I, and the ␤ chain of ATP synthase. These data support an important role for lipid peroxidationderived protein modifications in Alzheimer disease pathogenesis.

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Section: Discussionmentioning

confidence: 94%

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

Pamplona

Dalfó

Ayala

et al. 2005

Journal of Biological Chemistry

257

242

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“…It is well known that APOE 4 is the major genetic risk factor for AD, and it is remarkable that one of its functions appears to be to directly mediate the accumulation of intracellular A␤. It has been reported that A␤ is internalized through the scavenger receptor for advanced glycation end products (RAGE), in neurons and microglia [117][118][119]. The binding of A␤ to RAGE in neurons initiated a cascade of events that produces oxidative stress and nuclear factor-B (NF-B) activation, which induce the production of macrophage colony-stimulating factor [120] and an enhanced microglial response.…”

Section: Intracellular A␤ Oligomer Toxicitymentioning

confidence: 99%

“…The binding of A␤ to RAGE in neurons initiated a cascade of events that produces oxidative stress and nuclear factor-B (NF-B) activation, which induce the production of macrophage colony-stimulating factor [120] and an enhanced microglial response. Additionally, it has been shown that RAGE-A␤ complexes are internalized and that they co-localize with the lysosomal pathway in astrocytes in AD patients [119].…”

Section: Intracellular A␤ Oligomer Toxicitymentioning

confidence: 99%

Molecular Mechanisms of Amyloid Oligomers Toxicity

Kayed

Lasagna‐Reeves

2012

JAD

324

283

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Abstract. Amyloid oligomers have emerged as the most toxic species of amyloid-␤ (A␤). This hypothesis might explain the lack of correlation between amyloid plaques and memory impairment or cellular dysfunction. However, despite the numerous published research articles supporting the critical role A␤ oligomers in synaptic dysfunction and cell death, the exact definition and mechanism of amyloid oligomers formation and toxicity still elusive. Here we review the evidence supporting the many molecular mechanisms proposed for amyloid oligomers toxicity and suggest that the complexity and dynamic nature of amyloid oligomers may be responsible for the discrepancy among these mechanisms and the proposed cellular targets for amyloid oligomers.

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“…Using these culture cells, we could identify RAGE in SFMs by immunoblot analysis ( Figure 5). Human brain extract was used as a positive control, with a band observed at ϳ50 kd (34).…”

mentioning

confidence: 99%

High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine

Taniguchi¹,

Kikuchi²,

Yone³

et al. 2003

Arthritis & Rheumatism

431

364

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Objective. High mobility group box chromosomal protein 1 (HMGB-1), a nuclear DNA binding protein, was recently rediscovered as a new proinflammatory cytokine. The purpose of this study was to demonstrate HMGB-1 expression in vivo and to identify the role of HMGB-1 in the pathogenesis of rheumatoid arthritis (RA).Methods. HMGB-1 concentrations in synovial fluid (SF) and serum from RA and osteoarthritis (OA) patients were measured by immunoblot analysis. The protein's specific receptor, receptor for advanced glycation end products (RAGE), was examined in SF macrophages (SFMs). We measured levels of proinflammatory cytokines released by SFMs treated with HMGB-1 via enzyme-linked immunosorbent assay and used soluble RAGE (sRAGE) to block the release of tumor necrosis factor ␣ (TNF␣). Immunohistochemical analysis and immunofluorescence assay were employed to examine localization of HMGB-1 in RA synovium and its translocation in SFMs after TNF␣ stimulation.Results. HMGB-1 concentrations were significantly higher in SF of RA patients than in that of OA patients. SFMs expressed RAGE and released TNF␣, interleukin-1␤ (IL-1␤), and IL-6 upon stimulation with HMGB-1. HMGB-1 was found in CD68-positive cells of RA synovium, and TNF␣ stimulation translocated HMGB-1 from the nucleus to the cytosol in SFMs. Blockade by sRAGE inhibited the release of TNF␣ from SFMs.Conclusion. HMGB-1 was more strongly expressed in SF of RA patients than in that of OA patients, inducing the release of proinflammatory cytokines from SFMs. HMGB-1 plays a pivotal role in the pathogenesis of RA and may be an original target of therapy as a novel cytokine.High mobility group box chromosomal protein 1 (HMGB-1) has 219 residues in its primary amino acid sequence, and there is Ͼ98% sequence identity between the HMGB-1 of rodents and that of humans (1-6). In most cells, HMGB-1 is located in the nucleus. It is an abundant, highly conserved cellular protein and is widely known as a nuclear DNA binding protein that stabilizes nucleosome formation (7,8), facilitates gene transcription, and regulates the activity of steroid hormone receptors (9,10). However, it has been reported that HMGB-1 might be translocated from the nucleus to the cytosol and then released extracellularly.A previous study demonstrated that extracellular HMGB-1 induces the production of proinflammatory cytokines in macrophages (11). When released by activated monocytes, it participates in the development of lethality and activates downstream cytokine release. Furthermore, like other cytokine mediators of endotoxemia, HMGB-1 activates proinflammatory cytokine re-

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Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease

Cited by 242 publications

References 24 publications

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

Molecular Mechanisms of Amyloid Oligomers Toxicity

High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine

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