Ligands of Receptor for Advanced Glycation End-Products Produced by Activated Microglia are Critical in Neurodegenerative Diseases

Son, Myeongjoo; Oh, Seyeon; Lee, So Jung; Byun, Kyunghee

doi:10.4172/2161-0460.1000318

Cited by 4 publications

(3 citation statements)

References 51 publications

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“…HMGB1 release from various cells, including astrocytes and microglia, contributes to AD via its binding to RAGE, which activates inflammatory responses [ 71 , 72 ]. Upon interactions, Aβ and HMGB1 activate the NF-κB pathway [ 73 , 74 , 75 ]. RAGE induced-activation of NF-κB promotes the expression of proinflammatory cytokines, which induces a prolonged activation and promotion of signaling mechanisms for cell damage and regulates NLRP3 inflammasome activation [ 76 , 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Oleocanthal-Low EVOO and Oleocanthal against Amyloid-β and Related Pathology in a Mouse Model of Alzheimer’s Disease

et al. 2023

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Alzheimer’s disease (AD) is characterized by several pathological hallmarks, including the deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier (BBB) dysfunction, and neuroinflammation. Growing evidence support the neuroprotective effects of extra-virgin olive oil (EVOO) and oleocanthal (OC). In this work, we aimed to evaluate and compare the beneficial effects of equivalent doses of OC-low EVOO (0.5 mg total phenolic content/kg) and OC (0.5 mg OC/kg) on Aβ and related pathology and to assess their effect on neuroinflammation in a 5xFAD mouse model with advanced pathology. Homozygous 5xFAD mice were fed with refined olive oil (ROO), OC-low EVOO, or OC for 3 months starting at the age of 3 months. Our findings demonstrated that a low dose of 0.5 mg/kg EVOO-phenols and OC reduced brain Aβ levels and neuroinflammation by suppressing the nuclear factor-κB (NF-κB) pathway and reducing the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes. On the other hand, only OC suppressed the receptor for advanced glycation endproducts/high-mobility group box 1 (RAGE/HMGB1) pathway. In conclusion, our results indicated that while OC-low EVOO demonstrated a beneficial effect against Aβ-related pathology in 5xFAD mice, EVOO rich with OC could provide a higher anti-inflammatory effect by targeting multiple mechanisms. Collectively, diet supplementation with EVOO or OC could prevent, halt progression, and treat AD.

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Section: Discussionmentioning

confidence: 99%

Comparison of Oleocanthal-Low EVOO and Oleocanthal against Amyloid-β and Related Pathology in a Mouse Model of Alzheimer’s Disease

et al. 2023

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“…Collectively, the above findings suggest that OLE reduced neuroinflammation by suppressing the NF-κB pathway, which regulates RAGE/HGMB1 and NLRP3 inflammasome pathways. Besides its role in the entry of peripheral Aβ to the brain across the BBB, RAGE acts as a receptor of inflammation expressed on the astrocytes, which is also expressed in neurons and microglia. , RAGE is highly expressed in activated astrocytes, which induces neuroinflammation by releasing a high level of inflammatory cytokines. , PAMP and DAMP ligands such as Aβ and HMGB1 have been shown to interact and increase the expression and activity of RAGE. ,,, Several studies reported that the RAGE/NF-κB signaling pathway is involved in AD surrounding Aβ plaques, − and reported the implication of HMGB1 in AD pathology upon its release from various cells including astrocytes and microglia through its binding to RAGE, thus activating the inflammatory response. , Upon the interaction with RAGE, Aβ and HMGB1 activate several inflammatory signaling pathways, including NF-κB, which lead to cell death. , A study in 5xFAD mice at 6 months of age showed that RAGE induced the activation of NF-κB and initiated inflammatory response . Furthermore, NF-κB activation promotes the expression of pro-inflammatory cytokines to induce a prolonged activation and promotion of signaling mechanisms for cell damage and regulates NLRP3 inflammasome activation. − NLRP3 inflammasome processes pro-IL-1β to mature and functional IL-1β.…”

Section: Resultsmentioning

confidence: 99%

“…74,75 Upon the interaction with RAGE, Aβ and HMGB1 activate several inflammatory signaling pathways, including NF-κB, which lead to cell death. 76,77 A study in 5xFAD mice at 6 months of age showed that RAGE induced the activation of NF-κB and initiated inflammatory response. 57 Furthermore, NF-κB activation promotes the expression of pro-inflammatory cytokines to induce a prolonged activation and promotion of signaling mechanisms for cell damage and regulates NLRP3 inflammasome activation.…”

Section: ■ Introductionmentioning

confidence: 99%

Oleuropein-Rich Olive Leaf Extract Attenuates Neuroinflammation in the Alzheimer’s Disease Mouse Model

Abdallah

Al-Shami

Yang

et al. 2022

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is the most common form of dementia among several neurodegenerative disorders afflicting the elderly. AD is characterized by the deposition of extracellular amyloid-β (Aβ) plaques, disrupted blood−brain barrier (BBB), and neuroinflammation. Several studies have demonstrated the health benefits of olive oil and olive leaf extract (OLE) due to their polyphenolic content. The main phenolic compound in OLE is glycosylated oleuropein (OLG), while the aglycon form of oleuropein (OLA) exists in much lower amounts. This work aimed to evaluate the effect of a low dose of OLG-rich OLE and the mechanism(s) that contributed to the observed beneficial effects against Aβ pathology in the homozygous 5xFAD mouse model. Mice were fed with OLE-enriched diet (695 μg/kg body weight/day) for 3 months, starting at 3 months old. Overall findings demonstrated that OLE reduced neuroinflammation by inhibiting the NF-κB pathway and suppressing the activation of NLRP3 inflammasomes and RAGE/HMGB1 pathways. In addition, OLE reduced total Aβ brain levels due to increased clearance and reduced production of Aβ and enhanced BBB integrity and function, which collectively improved the memory function. Thus, the consumption of OLE as a dietary supplement is expected to stop and/or slow the progression of AD.

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AGE–RAGE stress: a changing landscape in pathology and treatment of Alzheimer’s disease

Prasad

2019

Mol Cell Biochem

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Ligands of Receptor for Advanced Glycation End-Products Produced by Activated Microglia are Critical in Neurodegenerative Diseases

Cited by 4 publications

References 51 publications

Comparison of Oleocanthal-Low EVOO and Oleocanthal against Amyloid-β and Related Pathology in a Mouse Model of Alzheimer’s Disease

Comparison of Oleocanthal-Low EVOO and Oleocanthal against Amyloid-β and Related Pathology in a Mouse Model of Alzheimer’s Disease

Oleuropein-Rich Olive Leaf Extract Attenuates Neuroinflammation in the Alzheimer’s Disease Mouse Model

AGE–RAGE stress: a changing landscape in pathology and treatment of Alzheimer’s disease

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