The Complexity of Sporadic Alzheimer’s Disease Pathogenesis: The Role of RAGE as Therapeutic Target to Promote Neuroprotection by Inhibiting Neurovascular Dysfunction

Perrone, Lorena; Sbai, Oualid; Nawroth, Peter P.; Bierhaus, Angelika

doi:10.1155/2012/734956

Cited by 39 publications

(49 citation statements)

References 100 publications

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“…AGEs are risk factors for AD 507 because they induce oxidative stress and inflamma-508 tion [1,16]. In agreement, our results indicate that the 509 MeDi helps prevent AD also because it leads to lower …”

supporting

confidence: 59%

“…Alzheimer's disease (AD) is the main cause of 27 dementia among the elderly, affecting more than 25 28 million people in the world [1]. A major health ans of consumption in the population.…”

Section: Introductionmentioning

confidence: 99%

“…Oxidative stress is a major risk factor for AD pro-506 gression [1,16,46,47]. AGEs are risk factors for AD 507 because they induce oxidative stress and inflamma-508 tion [1,16].…”

mentioning

confidence: 99%

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Observational and Ecological Studies of Dietary Advanced Glycation End Products in National Diets and Alzheimer's Disease Incidence and Prevalence

Perrone

Grant

2015

JAD

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supporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Observational and Ecological Studies of Dietary Advanced Glycation End Products in National Diets and Alzheimer's Disease Incidence and Prevalence

Perrone

Grant

2015

JAD

Self Cite

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“…In vitro studies have demonstrated that Aβ has nutritional value for cultured hippocampal neurons, as well as being toxic to these cells. The role that Aβ assumes depends on two factors, which include the maturity of neurons and the concentration of Aβ (14,16). A high concentration of Aβ triggers the toxic property, causing a loss of mature neurons and inhibition of axon growth.…”

Section: Discussionmentioning

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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“…RAGE triggers intracellular signaling pathways via PI3K and MAPK, which culminate in the activation of the transcription factor NFκB and subsequent transcription of IL-1β [68]. RAGE-null mice have both diminished transcription and secretion of IL-1β in response to tobacco smoke exposure, a known contributor of oxidative stress and inflammation [69].…”

Section: Il-1β and Rage In Acute And Chronic Inflammatory And Metabolic Resmentioning

confidence: 99%

Il-1β, Rage and Fabp4: Targeting the Dynamic Trio in Metabolic Inflammation and Related Pathologies

Hardaway

Podgorski

2013

Future Med. Chem.

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Within the past decade, inflammatory and lipid mediators, such as IL-1β, FABP4 and RAGE, have emerged as important contributors to metabolic dysfunction. As growing experimental and clinical evidence continues to tie obesity-induced chronic inflammation with dysregulated lipid, insulin signaling and related pathologies, IL-1β, FABP4 and RAGE each are being independently implicated as culprits in these events. There are also convincing data that molecular pathways driven by these molecules are interconnected in exacerbating metabolic consequences of obesity. This article highlights the roles of IL-1β, FABP4 and RAGE in normal physiology as well as focusing specifically on their contribution to inflammation, insulin resistance, atherosclerosis, Type 2 diabetes and cancer. Studies implicating the interconnection between these pathways, current and emerging therapeutics, and their use as potential biomarkers are also discussed. Evidence of impact of IL-1β, FABP4 and RAGE pathways on severity of metabolic dysfunction underlines the strong links between inflammatory events, lipid metabolism and insulin regulation, and offers new intriguing approaches for future therapies of obesity-driven pathologies.

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The Complexity of Sporadic Alzheimer’s Disease Pathogenesis: The Role of RAGE as Therapeutic Target to Promote Neuroprotection by Inhibiting Neurovascular Dysfunction

Cited by 39 publications

References 100 publications

Observational and Ecological Studies of Dietary Advanced Glycation End Products in National Diets and Alzheimer's Disease Incidence and Prevalence

Observational and Ecological Studies of Dietary Advanced Glycation End Products in National Diets and Alzheimer's Disease Incidence and Prevalence

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

Il-1β, Rage and Fabp4: Targeting the Dynamic Trio in Metabolic Inflammation and Related Pathologies

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