Role of RAGE in the Pathogenesis of Neurological Disorders

Juranek, Judyta K.; Mukherjee, Konark; Kordas, Bernard; Załęcki, Michał; Korytko, Agnieszka; Zglejc-Waszak, Kamila; Szuszkiewicz, Jarosław; Banach, Marta

doi:10.1007/s12264-022-00878-x

Cited by 24 publications

(33 citation statements)

References 130 publications

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“…In addition, TLR2 and TLR4 are important members in brain innate immune response system and expressed on the membranes of microglia, astrocytes, neurons, and endothelial cells [ 55 ]. RAGE is also expressed under normal physiological conditions in neurons, immune cells, activated endothelial cells, glia cells, and vascular smooth muscle cells [ 56 ], and activation of RAGE could also induce the expression and secretion of the pro-inflammatory and proapoptotic mediators to work in concert with TLR2, TLR4, and RAGE to exacerbate brain damage [ 57 , 58 ]. More comprehensive work is warranted and will help to advance our understanding of the pathogenesis of RIBI and provide new strategies for better prevention and control of the disease.…”

Section: Discussionmentioning

confidence: 99%

Pregabalin mitigates microglial activation and neuronal injury by inhibiting HMGB1 signaling pathway in radiation-induced brain injury

Zhang

Jiang

et al. 2022

J Neuroinflammation

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Background Radiation-induced brain injury (RIBI) is the most serious complication of radiotherapy in patients with head and neck tumors, which seriously affects the quality of life. Currently, there is no effective treatment for patients with RIBI, and identifying new treatment that targets the pathological mechanisms of RIBI is urgently needed. Methods Immunofluorescence staining, western blotting, quantitative real-time polymerase chain reaction (Q-PCR), co-culture of primary neurons and microglia, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and CRISPR–Cas9-mediated gene editing techniques were employed to investigate the protective effects and underlying mechanisms of pregabalin that ameliorate microglial activation and neuronal injury in the RIBI mouse model. Results Our findings showed that pregabalin effectively repressed microglial activation, thereby reducing neuronal damage in the RIBI mouse model. Pregabalin mitigated inflammatory responses by directly inhibiting cytoplasmic translocation of high-mobility group box 1 (HMGB1), a pivotal protein released by irradiated neurons which induced subsequent activation of microglia and inflammatory cytokine expression. Knocking out neuronal HMGB1 or microglial TLR2/TLR4/RAGE by CRISPR/Cas9 technique significantly inhibited radiation-induced NF-κB activation and pro-inflammatory transition of microglia. Conclusions Our findings indicate the protective mechanism of pregabalin in mitigating microglial activation and neuronal injury in RIBI. It also provides a therapeutic strategy by targeting HMGB1-TLR2/TLR4/RAGE signaling pathway in the microglia for the treatment of RIBI.

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Section: Discussionmentioning

confidence: 99%

Pregabalin mitigates microglial activation and neuronal injury by inhibiting HMGB1 signaling pathway in radiation-induced brain injury

Zhang

Jiang

et al. 2022

J Neuroinflammation

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“…In addition, biopsies of the gastrocnemius and femoral nerves in type 2 diabetes patients revealed significant increases in the deposition of AGEs in the axons and myelin sheaths, and these AGEs could bind to RAGE highly expressed on the micro-vessels at the nerve bundle membrane, nerve inner membrane, and nerve outer membrane. This leads to activation of the NF-κB pathway and an increase in the release of inflammatory factors such as IL-6 and IL-8, which triggers an inflammatory response that interferes with the normal functions of blood vessels and leads to inflammatory vascular neuropathy [ 75 ]. Of note, the diabetic vasculature is stimulated by the long-term presence of high glucose concentrations.…”

Section: The Pathological Process Of Dusmentioning

confidence: 99%

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

Wei

et al. 2023

Biomater Res

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Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. Graphical Abstract This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

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“…To date, clinical trials on the use of arundic acid or sRAGE have only been conducted in patients with neurodegenerative diseases. Further studies are required in TBI patients to gain a more in-depth understanding of the S100B/RAGE signaling modulation and to determine the therapeutic dose for a pharmaceutical manipulation of RAGE [ 143 ]. The targeting of cerebral cells by drugs interacting with the S100/RAGE pathway is a pharmacological challenge.…”

Section: S100b As a Putative Therapeutic Targetmentioning

confidence: 99%

S100B, Actor and Biomarker of Mild Traumatic Brain Injury

Oris

Kahouadji

Durif³

et al. 2023

IJMS

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Mild traumatic brain injury (mTBI) accounts for approximately 80% of all TBI cases and is a growing source of morbidity and mortality worldwide. To improve the management of children and adults with mTBI, a series of candidate biomarkers have been investigated in recent years. In this context, the measurement of blood biomarkers in the acute phase after a traumatic event helps reduce unnecessary CT scans and hospitalizations. In athletes, improved management of sports-related concussions is also sought to ensure athletes’ safety. S100B protein has emerged as the most widely studied and used biomarker for clinical decision making in patients with mTBI. In addition to its use as a diagnostic biomarker, S100B plays an active role in the molecular pathogenic processes accompanying acute brain injury. This review describes S100B protein as a diagnostic tool as well as a potential therapeutic target in patients with mTBI.

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Role of RAGE in the Pathogenesis of Neurological Disorders

Cited by 24 publications

References 130 publications

Pregabalin mitigates microglial activation and neuronal injury by inhibiting HMGB1 signaling pathway in radiation-induced brain injury

Pregabalin mitigates microglial activation and neuronal injury by inhibiting HMGB1 signaling pathway in radiation-induced brain injury

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

S100B, Actor and Biomarker of Mild Traumatic Brain Injury

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