34-752: [REDACTED] Look up ager in Wiktionary, the free dictionary. Ager or AGER may refer to: Ager (surname) Places [ edit ] Ager (river) , a river in Upper Austria Àger , a municipality in Catalonia, Spain Viscounty of Àger , a medieval Catalan jurisdiction that branched off the County of Urgell Ager, California , unincorporated community Ager Romanus , Latin term for
68-538: A class of ligands through a common structural motif , RAGE is often referred to as a pattern recognition receptor . RAGE also has at least one other agonistic ligand: high mobility group protein B1 ( HMGB1 ). HMGB1 is an intracellular DNA-binding protein important in chromatin remodeling which can be released by necrotic cells passively, and by active secretion from macrophages , natural killer cells , and dendritic cells . The interaction between RAGE and its ligands
102-566: A crucial role in limiting the negative impacts of AGEs on vascular and metabolic health. 3. 80 K-H Phosphoprotein (Protein Kinase C Substrate) (AGE- R2 ): The 80 K-H phosphoprotein, also known as protein kinase C substrate (AGE-R2), is involved in the intracellular signaling response to AGE exposure. AGE-R2 plays a role in regulating pathways that help cells adapt to oxidative stress by modulating protein kinase C (PKC) activity. This regulation aids in maintaining cellular homeostasis and mitigating
136-551: A dvanced g lycation e ndproducts) , also called AGER , is a 35 kilodalton transmembrane receptor of the immunoglobulin super family which was first characterized in 1992 by Neeper et al. Its name comes from its ability to bind advanced glycation endproducts ( AGE ), which include chiefly glycoproteins , the glycans of which have been modified non- enzymatically through the Maillard reaction . In view of its inflammatory function in innate immunity and its ability to detect
170-399: A medieval Catalan jurisdiction that branched off the County of Urgell Ager, California , unincorporated community Ager Romanus , Latin term for the territory surrounding and outside the city of Rome Other [ edit ] A US Navy hull classification symbol: Environmental research ship (AGER) , actually a signals intelligence collection vessel AGER, an alternate name for
204-416: A role in modulating inflammatory signaling pathways, thereby contributing to the regulation of tissue homeostasis and preventing chronic inflammation caused by AGE accumulation. 2. OST -48 (Oligosaccharyl Transferase-4) (AGE-R1): OST-48, commonly referred to as AGE-R1, is involved in detoxifying and preventing the accumulation of AGEs, especially under conditions such as diabetes. The expression of OST-48
238-664: A role in the removal of AGE rather than in signal transduction as is the case for RAGE. Other AGE receptors are: 1. SR-A (Macrophage Scavenger Receptor Type I and II): SR-A, also known as macrophage scavenger receptor Type I and II, is primarily expressed on macrophages. These receptors play an important role in recognizing and clearing modified proteins such as AGEs from circulation. The binding of AGEs to SR-A triggers internalization and degradation, effectively reducing oxidative stress within tissues. Upon ligand binding, SR-A activates downstream signaling pathways that promote phagocytosis and lysosomal degradation. This receptor also plays
272-463: A transmembrane domain that anchors the receptor to the cell membrane, and an intracellular domain essential for signaling. In contrast, the soluble form (sRAGE) consists only of the extracellular domains and lacks both the transmembrane and intracellular domains. sRAGE can be produced by two different mechanisms: either through alternative splicing of the RAGE gene, leading to a truncated form that lacks
306-498: Is able to bind several ligands and therefore is referred to as a pattern-recognition receptor. Ligands which have so far been found to bind RAGE are: The receptor for advanced glycation end products (RAGE) is a multiligand member of the immunoglobulin superfamily, originally identified due to its ability to bind advanced glycation end products (AGEs). AGEs accumulate in various chronic conditions such as diabetes and renal failure. However, RAGE also binds other ligands, notably proteins of
340-427: Is different from Wikidata All article disambiguation pages All disambiguation pages ager [REDACTED] Look up ager in Wiktionary, the free dictionary. Ager or AGER may refer to: Ager (surname) Places [ edit ] Ager (river) , a river in Upper Austria Àger , a municipality in Catalonia, Spain Viscounty of Àger ,
374-838: Is different from Wikidata All article disambiguation pages All disambiguation pages RAGE (receptor) 2ENS , 2M1K , 2LE9 , 4LP5 , 2MOV , 3O3U , 2LMB , 4LP4 , 4OF5 , 4OI8 , 4XYN , 2MJW , 2E5E , 2L7U , 3CJJ , 4OFV , 4P2Y , 4OI7 , 4YBH ,%%s 1PWI , 2BJP , 2E5E , 2ENS , 2L7U , 2LE9 , 2LMB , 2M1K , 2MJW , 2MOV , 3CJJ , 3O3U , 4LP4 , 4LP5 , 4OF5 , 4OFV , 4OI7 , 4OI8 , 4P2Y , 4XYN 177 11596 ENSG00000204305 ENSG00000230514 ENSMUSG00000015452 Q15109 Q62151 NM_001206940 NM_001206954 NM_001206966 NM_172197 NM_001271422 NM_001271423 NM_001271424 NM_007425 NP_001193869 NP_001193883 NP_001193895 NP_751947 NP_001258351 NP_001258352 NP_001258353 NP_031451 RAGE ( r eceptor for
SECTION 10
#1732772260244408-510: Is expressed in tissues such as the liver, vascular smooth muscle cells, and neurons. LRP1 functions by promoting the cellular uptake of AGE-modified proteins, thereby preventing their accumulation and reducing oxidative damage. The receptor also interacts with signaling pathways that regulate inflammation, making it an important factor in protecting against AGE-induced vascular and metabolic complications. 9. MSR1 (Macrophage Scavenger Receptor 1) : MSR1, also known as class A scavenger receptor,
442-412: Is expressed on endothelial cells, smooth muscle cells, and macrophages, and plays a key role in mediating endothelial dysfunction and promoting atherosclerotic plaque formation. The binding of AGEs to LOX-1 activates signaling pathways, including reactive oxygen species (ROS) production and NF-κB activation, which contribute to vascular inflammation and dysfunction. This makes LOX-1 a significant mediator in
476-515: Is expressed primarily on macrophages and plays a crucial role in the phagocytic uptake of AGEs. By recognizing and internalizing AGE-modified proteins, MSR1 helps reduce inflammation and cellular stress in tissues exposed to AGEs. This receptor is involved in activating pro-inflammatory signaling pathways, but it also contributes to tissue repair and the resolution of inflammation, helping maintain tissue homeostasis. 10. FEEL-1/CLEC14A (Facultative Endothelial Lectin-1): FEEL-1, also known as CLEC14A,
510-445: Is involved in activating signaling pathways such as MAPK and Toll-like receptor 4 (TLR4), which help modulate the inflammatory response to AGEs, thus preventing chronic inflammation and tissue damage. 7. SR-BI (Scavenger Receptor Class B Type I) : SR-BI is primarily known for its role in cholesterol transport but also binds AGEs. It is expressed on various cell types, including liver cells and endothelial cells, where it facilitates
544-496: Is regulated by cellular stress responses, particularly oxidative stress, which often coincides with elevated AGE levels. OST-48 contributes to reducing AGE-induced cellular toxicity by facilitating the breakdown of AGEs into less harmful by-products. The receptor interacts with various signaling molecules, such as peroxisome proliferator-activated receptor gamma (PPAR-γ), which assists in mitigating cellular stress responses and restoring metabolic balance. This detoxification process plays
578-410: Is thought to influence disease outcomes. An excess of mRAGE is often associated with inflammation and disease progression, whereas higher concentrations of sRAGE may be beneficial in mitigating inflammatory responses. The distinct structure of RAGE makes it a potential target for therapeutic intervention, particularly in conditions involving chronic inflammation. Inhibitors that prevent ligand binding to
612-484: Is thought to result in pro- inflammatory gene activation. Due to an enhanced level of RAGE ligands in diabetes or other chronic disorders, this receptor is hypothesised to have a causative effect in a range of inflammatory diseases such as diabetic complications, Alzheimer's disease and even some tumors . Isoforms of the RAGE protein, which lack the transmembrane and the signaling domain (commonly referred to as soluble RAGE or sRAGE) are hypothesized to counteract
646-628: The PBX2 gene. About 30 polymorphisms are known most of which are single-nucleotide polymorphisms . The primary transcript of the human RAGE gene ( pre-mRNA ) is thought to be alternatively spliced . So far about 6 isoforms including the full length transmembrane receptor have been found in different tissues such as lung, kidney, brain etc. Five of these 6 isoforms lack the transmembrane domain and are thus believed to be secreted from cells. Generally these isoforms are referred to as sRAGE (soluble RAGE) or esRAGE ( endogenous secretory RAGE). One of
680-731: The S100/calgranulin family, such as EN-RAGE and S100B, which play significant roles in inflammatory processes. RAGE ligands interact with the receptor through its extracellular domain, triggering a cascade of intracellular signaling pathways. These pathways lead to the activation of key transcription factors like nuclear factor kappa B (NF-κB), which is central to the expression of proinflammatory cytokines, adhesion molecules (such as VCAM-1 and ICAM-1), and other mediators of inflammation. Upon binding ligands like EN-RAGE or S100B, RAGE stimulates various inflammatory responses, including endothelial cell activation, mononuclear cell migration, and
714-423: The V domain have been studied to reduce downstream inflammatory signaling. Targeting the cytoplasmic domain to disrupt intracellular signal transduction is another approach being explored. Additionally, increasing the levels of sRAGE could serve as an effective strategy to neutralize pro-inflammatory ligands and limit their interaction with mRAGE, offering potential benefits in treating inflammatory conditions. RAGE
SECTION 20
#1732772260244748-411: The detrimental action of the full-length receptor and are hoped to provide a means to develop a cure against RAGE-associated diseases. The RAGE gene lies within the major histocompatibility complex ( MHC class III region) on chromosome 6 and comprises 11 exons interlaced by 10 introns. Total length of the gene is about 1400 base pairs (bp) including the promoter region, which partly overlaps with
782-433: The development of various inflammatory and metabolic conditions. The membrane-bound form of RAGE, commonly known as mRAGE, is a full-length receptor comprising several important structural domains: The soluble form of RAGE (sRAGE) only includes the extracellular domain and lacks both the transmembrane and cytoplasmic domains. sRAGE can be generated through two primary mechanisms: The balance between mRAGE and sRAGE levels
816-682: The harmful effects of AGEs on cellular structures, ultimately contributing to the cell's resilience against oxidative stress. 4. Galectin-3 (AGE-R3): Galectin-3, a member of the lectin family, is a multifunctional receptor that binds to AGEs and helps clear them from the extracellular space. This receptor is known for its involvement in modulating apoptosis, cell proliferation, and immune responses. Upon binding AGEs, Galectin-3 activates downstream signaling pathways, including those involving mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB), which are crucial for inflammatory regulation. By mediating these pathways, Galectin-3 reduces
850-462: The isoforms lacks the V-domain and is thus believed not to be able to bind RAGE ligands. RAGE exists in two primary forms in the body: a membrane-bound form known as mRAGE and a soluble form known as sRAGE. The membrane-bound form (mRAGE) consists of three key components: an extracellular region made up of three immunoglobulin-like domains (one variable V-type domain and two constant C-type domains),
884-532: The pro-inflammatory effects of AGE accumulation and helps maintain tissue integrity. Its role in regulating apoptosis and immune cell recruitment further contributes to limiting AGE-induced tissue damage, thus playing a protective role in chronic inflammatory and fibrotic conditions. 5. LOX-1 (Lectin-like Oxidized Low-Density Lipoprotein Receptor-1): LOX-1 is primarily known for binding oxidized low-density lipoproteins (oxLDL) but also binds AGEs. It
918-611: The production of cytokines such as TNF-α and IL-1β. These interactions between RAGE and its ligands contribute to chronic inflammatory conditions, including atherosclerosis, Alzheimer's disease, and diabetic complications. Inhibiting the RAGE-ligand interaction—through the use of soluble RAGE (sRAGE) or specific antibodies—can suppress these inflammatory responses, offering potential therapeutic strategies. Besides RAGE there are other receptors which are believed to bind advanced glycation endproducts. However, these receptors could play
952-462: The progression of vascular complications, particularly in metabolic disorders like diabetes. 6. CD36 : CD36 is an important scavenger receptor expressed on macrophages, endothelial cells, and adipocytes, and it plays a major role in the recognition and uptake of AGE-modified proteins. CD36 facilitates the clearance of AGEs, thereby reducing oxidative stress and inflammation. It also contributes to lipid metabolism and immune regulation. The receptor
986-673: The protein RAGE (receptor) See also [ edit ] Agir (disambiguation) Aegir (disambiguation) Agar (disambiguation) Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title Ager . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=Ager&oldid=1259122584 " Category : Disambiguation pages Hidden categories: Misplaced Pages indefinitely move-protected pages Short description
1020-454: The same term [REDACTED] This disambiguation page lists articles associated with the title Ager . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=Ager&oldid=1259122584 " Category : Disambiguation pages Hidden categories: Misplaced Pages indefinitely move-protected pages Short description
1054-541: The schematics attached) These effects are particularly significant in the progression of several chronic diseases, such as diabetes, cardiovascular diseases, neurodegenerative disorders, and cancer. The full RAGE receptor plays an important role in cellular communication, interacting with a diverse set of ligands, including advanced glycation end products (AGEs), amyloid-β peptides, and S100 proteins. These interactions activate multiple downstream signaling pathways that contribute to cellular stress responses and are linked to
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1088-413: The territory surrounding and outside the city of Rome Other [ edit ] A US Navy hull classification symbol: Environmental research ship (AGER) , actually a signals intelligence collection vessel AGER, an alternate name for the protein RAGE (receptor) See also [ edit ] Agir (disambiguation) Aegir (disambiguation) Agar (disambiguation) Topics referred to by
1122-518: The transmembrane and cytosolic regions, or through proteolytic cleavage of mRAGE by specific enzymes such as ADAM10 or matrix metalloproteinases (MMPs). Upon ligand binding, mRAGE recruits the intracellular protein DIAPH1 (Diaphanous-related formin-1), which is critical for initiating intracellular signaling. This signaling cascade can result in pathological outcomes, including oxidative stress, inflammation, cellular dysfunction, and apoptosis. (Refer to
1156-511: The uptake of AGE-modified proteins. By mediating the clearance of AGEs, SR-BI helps mitigate oxidative stress and maintain lipid homeostasis. Its role in lipid metabolism also supports the reduction of AGE-induced cellular damage, contributing to overall vascular health. 8. LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) : LRP1 is involved in the endocytosis and degradation of various ligands, including AGEs. It
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