Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease

Srikanth, Velandai; Maczurek, Annette; Phan, Thanh G.; Steele, Megan L.; Westcott, Bernadette; Juskiw, Damian; Münch, Gerald

doi:10.1016/j.neurobiolaging.2009.04.016

Cited by 429 publications

(293 citation statements)

References 126 publications

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“…Since RAGE induction is under the effect of AGEs, the RAGE-AGEs pathway is thought to be incriminated in the pathogenesis of these diseases. [20,21] Receptor for advanced glycation end products is a receptor for a family of about 20 related calciumbinding proteins that are only expressed in vertebrates. These include the S100s, which are cells that alter several intracellular functions.…”

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confidence: 99%

A Soluble Receptor for Advanced Glycation End Product Levels in Patients with Systemic Lupus Erythematosus

2013

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Amaç: Bu çalışmada sistemik lupus eritematöz (SLE) olan hastalarda ileri glikasyon son ürünlerinin çözünür reseptörünün (sRAGE) plazma düzeyleri değerlendirildi ve bu düzeylerin farklı klinik, laboratuvar ve tedavi parametreleri ile olan ilişkisi araştırıldı. Hastalar ve yöntemler:Çalışmaya toplam 120 SLE hastası (111 kadın, 9 erkek) ve yaş ve cinsiyet eşleştirmeli 40 sağlıklı kontrol alındı. Plazma sRAGE düzeyleri, ticari olarak satılan enzim bağlı immünosorbent test (ELISA) kiti kullanılarak ölçüldü. Plazma sRAGE düzeyleri ve SLE'nin klinik ve laboratuvar özellikleri arasındaki muhtemel ilişki de değerlendirildi. Farklı tedavi yöntemlerinin sRAGE plazma düzeyleri üzerindeki etkinliği incelendi. Bulgular: Sağlıklı kontrollere kıyasla, SLE hastalarının plazma sRAGE düzeyleri anlamlı düzeyde daha düşüktü (p=0.003). Cilt döküntüsü veya serozit olan hastaların sRAGE düzeyleri, olmayanlara kıyasla anlamlı düzeyde daha yüksekti (sırasıyla p=0.036 ve p=0.017). Daha uzun süre tedavi edilen SLE hastalarının sRAGE düzeyleri, daha kısa süreli tedavi edilenlerden daha yüksekti (p=0.000). Kortikosteroid ile tedavi edilen ve kombine tedavi edilen hastalar arasında düzey açısından anlamlı bir fark yoktu (p=0.89). sRAGE düzeyleri ve total beyaz kan hücre (WBC) sayımı (r=-0.356; p=0.003), lenfosit (r=0.341; p<0.001) ve nötrofil (r=0.289; p=0.006) arasında anlamlı negatif bir ilişki vardı.Sonuç: Çalışmamızda SLE hastalarında sRAGE plazma düzeylerinin anlamlı derecede azaldığı bulundu. Bu da, sRAGE düzeylerinin hastalığın patogenezinde muhtemel bir rol oynadığını göstermektedir.Anahtar sözcükler: İleri glikasyon son ürünü; reseptör; sistemik lupus eritematöz. Objectives:In this study, we aimed to evaluate the plasma levels of a soluble receptor for advanced glycation end products (sRAGE) in patients with systemic lupus erythematosus (SLE) and to investigate their relationship with different clinical, laboratory, and therapeutic parameters. Patients and methods:A total of 120 patients with SLE (111 females, 9 males) and 40 age-and gender-matched healthy controls were included. The plasma sRAGE levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The possible relationship between plasma sRAGE levels with SLE clinical and laboratory characteristics were also assessed. The effectiveness of different therapeutic modalities on plasma sRAGE levels was analyzed. Results:The SLE patients had significantly lower plasma levels of sRAGE than the healthy controls (p=0.003). The patients with a skin rash or serositis had significantly higher sRAGE levels than those without (p=0.036 and p=0.017, respectively). The SLE patients who were treated over a longer period of time showed higher levels of sRAGE than those treated for shorter periods (p=0.000). No significant difference in levels was found among the patients treated with corticosteroids and those treated with combined therapy (p=0.89). There was a significant negative correlation between the sRAGE level and the total white blood cell (WBC) count (...

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confidence: 99%

A Soluble Receptor for Advanced Glycation End Product Levels in Patients with Systemic Lupus Erythematosus

2013

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“…The protein is expressed at a high level in the nervous system during development. Induced expression is frequently associated with pathological stages, such as diabetic endothelial damage and AD (8,9,19).…”

Section: Discussionmentioning

confidence: 99%

“…Induced expression of RAGE is frequently correlated with pathological stages such as diabetic endothelial damage and AD (8,9). It has been proposed that RAGE is responsible for Aβ neurotoxicity (10).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic role of advanced glycation end-products in PC12 cells treated with β-amyloid peptide

Yan

Han

2013

Molecular Medicine Reports

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Abstract. Alzheimer's disease (AD) is the most common type of dementia afflicting the elderly. Recent studies have increasingly suggested that a high concentration of advanced glycation end products (AGEs) may be important in AD pathogenesis. However, the mechanisms and pathways involved remain unknown. The aim of this study was to explore whether the mechanism of the effect of AGEs on Aβ-PC12 cells [PC12 cells treated with β-amyloid (Aβ) peptide] was associated with oxidative stress; and to study whether inhibiting the activity of the receptor for AGE (RAGE) attenuated the toxic effect of AGEs and Aβ on PC12 cells. Several PC12 cells were pretreated with Aβ, and were then treated with different concentrations of AGEs. Other PC12 cells were treated with trypsin, a pancreatic protein enzyme and an inhibitor of RAGE, and were then treated with Aβ and AGEs. Apoptosis was measured by flow cytometry (FCM) and cell viability was measured by MTT assay. RAGE and nuclear factor-κB (NF-κB) were measured by reverse transcription-polymerase chain reaction (RT-PCR) assay. With an increase in AGE concentration, the viability of Aβ-PC12 cells treated with AGEs decreased. However, the Aβ-PC12 cell viability was greater in the trypsin group than in the non-trypsin group. Cell apoptosis rates and mRNA expression of RAGE and NF-κB in Aβ-PC12 cells treated with AGEs were significantly higher than in the Aβ-PC12 cells. AGEs and Aβ were neurotoxic, and RAGE triggered the neural cytotoxic role of AGEs in Aβ-PC12 cells. The molecular mechanisms may be connected with the expression of NF-κB and apoptosis mediated by RAGE. Inhibiting the activity of RAGE may mitigate the toxic effect of AGEs and Aβ on neural cells.

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“…Thus, RAGE downstream signaling activates several diverse cell activities, such as differentiation, proliferation, adhesion and migration [7,14,[21][22][23][24]. It is generally believed that RAGE-induced pathways are implicated in the development of several common diseases [15,[25][26][27][28][29]. This view is contradictory to data showing that the activation and upregulation of RAGE enhance cell survival in cases of cell dysfunction due to increased AGE levels, oxidative stress, etc.…”

Section: Introductionmentioning

confidence: 96%

Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

Marinakis

Bagkos

Piperi

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Lung cancer is one of the most common malignancies in the world and one of the leading causes of death from cancer. In the search for molecules that may be involved in lung tumor induction and progression, the receptor of advanced glycation end products (RAGE) comes across as a critical regulator of lung physiology. RAGE is a multiligand receptor that presents a differential expression pattern in lung epithelial cells compared to other cell types being gradually increased from fetal to birth and adult life. Under stress conditions, RAGE expression and activation are rapidly elevated resulting in chronic inflammation, which, in turn, in many instances, promotes epithelial cell malignant transformation. RAGE overexpression in normal lung alveolar type I epithelial cells is followed by rapid downregulation upon malignant transformation, being associated with increased aggressiveness. This is a striking paradox, since in every other cell type the pattern of RAGE expression follows the opposite direction, suggesting the involvement of RAGE in the well-functioning of lung cells. Additionally, RAGE has been attributed with the role of adhesion molecule, since it can stabilize mature alveolar epithelial cells to their substrate (basal lamina) by interacting electrostatically with other molecules. However, the reduction of RAGE observed in lung tumorigenesis interrupts cell-to-cell and cell-to-substrate communication, which is a critical step for cancer cell induction, progression and migration. This review addresses the differential properties of RAGE in lung physiology and carcinogenesis, providing evidence of therapeutic possibilities.

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Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease

Cited by 429 publications

References 126 publications

A Soluble Receptor for Advanced Glycation End Product Levels in Patients with Systemic Lupus Erythematosus

A Soluble Receptor for Advanced Glycation End Product Levels in Patients with Systemic Lupus Erythematosus

Cytotoxic role of advanced glycation end-products in PC12 cells treated with β-amyloid peptide

Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

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