Clinical Manifestation of AGE-RAGE Axis in Neurodegenerative and
                    Cognitive Impairment Disorders

Sabreena Naz; Tarique Mahmood; Ramesh Gupta; Mohammed Haris Siddiqui; Farogh Ahsan; Vaseem Ahamad Ansari; Arshiya Shamim; Ali Abbas Rizvi

doi:10.1055/a-2004-3591

Drug Research, Table of Contents

Drug Res (Stuttg) 2023; 73(06): 309-317
DOI: 10.1055/a-2004-3591

Review

Clinical Manifestation of AGE-RAGE Axis in Neurodegenerative and Cognitive Impairment Disorders

Sabreena Naz

¹Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India

,

Tarique Mahmood

¹Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India

,

Ramesh Gupta

²Department of Pharmacy, Hygia Institute of Pharmaceutical Education and Research, Lucknow, India

,

Mohammed Haris Siddiqui

³Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, India

,

Farogh Ahsan

¹Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India

,

Vaseem Ahamad Ansari

¹Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India

,

Arshiya Shamim

¹Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India

,

Ali Abbas Rizvi

¹Department of Pharmacy, Faculty of Pharmacy, Integral University, Lucknow, India

²Department of Pharmacy, Hygia Institute of Pharmaceutical Education and Research, Lucknow, India

› Author Affiliations

Abstract

The receptor of Advanced Glycation Endproducts (RAGE) and Advanced Glycation Endproducts (AGE) have multiple functions in our body and their restraint are being observed in neurodegenerative and memory impairment disorders. The review of different pathways allows an understanding of the probable mechanism of neurodegeneration and memory impairment involving RAGE and AGE. Commonly we observe AGE accumulation in neural cells and tissues but the extent of accumulation increases with the presence of memory impairment disorder. The presence of AGEs can also be seen in morbid accumulation, pathological structures in the form of amyloid clots, and nervous fibrillary tangles in Alzheimer’s Disease (AD) and memory impairment disease.

Many neuropathological and biochemical aspects of AD are explained by AGEs, including widespread protein crosslinking, glial activation of oxidative stress, and neuronal cell death. Oxidative stress is due to different reasons and glycation end products set in motion and form or define various actions which are normally due to AGE changes in a pathogenic cascade. By regulating the transit of ß-amyloid in and out of the brain or altering inflammatory pathways, AGE and it’s ensnare receptor such as soluble RAGE may function as blockage or shield AD development. RAGE activates the transcription-controlling factor Necrosis Factor (NF-κB) and increases the protraction of cytokines, like a higher number of Tumor Necrosis Factor (TNF-α) and Interleukin (IL-I) by inducing several signal transduction cascades. Furthermore, binding to RAGE can pro-activate reactive oxygen species (ROS), which is popularly known to cause neuronal death.

Key words

AGE-RAGE axis - Neurodegeneration - cognitive impairment - Parkinson - Alzheimer

Full Text

References

References
1 Goldin A, Beckman JA, Schmidt AM. et al. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006; 114: 597-605
2 Anzilotti S, Giampà C, Laurenti D. et al. Immunohistochemical localization of receptor for advanced glycation end (RAGE) products in the R6/2 mouse model of Huntington’s disease. Brain Res Bull 2012; 87: 350-358
3 Ashraf JM, Ahmad S, Choi I. et al. Recent advances in detection of AGEs: Immunochemical, bioanalytical and biochemical approaches. IUBMB Life 2015; 67: 897-913
4 Bayarsaikhan E, Bayarsaikhan D, Lee J, et al. Microglial AGE-albumin is critical for neuronal death in Parkinson’s disease: a possible implication for theranostics. Int J Nanomedicine 2016;10 Spec Iss:281–292
5 Deane R, Du Yan S, Submamaryan RK. et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9: 907-913
6 Bianchi R, Giambanco I, Donato R. S100B/RAGE-dependent activation of microglia via NF-kappaB and AP-1 Co-regulation of COX-2 expression by S100B, IL-1beta and TNF-alpha. Neurobiol Aging 2010; 31: 665-677
7 Bianchi R, Kastrisianaki E, Giambanco I. et al. S100B protein stimulates microglia migration via RAGE-dependent up-regulation of chemokine expression and release. J Biol Chem 2011; 286: 7214-7226
8 Braak H, Sastre M, Del Tredici K. et al. Development of alpha-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 2007; 114: 231-241
9 Buckley ST, Ehrhardt C. The Receptor for Advanced Glycation End Products (RAGE) and the lung. J Biomed Biotechnol 2010; 2010: 91740
10 Yan S, Chen X, Walker D. et al. RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer’s disease. Curr Mol Med 2007; 7: 735-742
11 Iłzecka J. Serum-soluble receptor for advanced glycation end product levels in patients with amyotrophic lateral sclerosis. Acta Neurol Scand 2009; 120: 119-122
12 Liang F, Jia J, Wang S. et al. Decreased plasma levels of soluble low-density lipoprotein receptor-related protein-1 (sLRP) and the soluble form of the receptor for advanced glycation end products (sRAGE) in the clinical diagnosis of Alzheimer’s disease. J Clin Neurosci 2013; 20: 357-361
13 Wang L, Li S, Jungalwala FB. The receptor for advanced glycation end products (RAGE) mediates neuronal differentiation and neurite outgrowth. J Neurosci Res 2008; 86: 1254-1266
14 Sorci G, Rizzi F, Giambanco I. et al. RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta 2013; 1833: 101-109
15 Deane R, Singh I, Sagare AP. et al. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer’s disease. J Clin Invest 2012; 122: 1377-1392
16 Ding Q, Keller JN. Evaluation of rage isoforms, ligands, and signaling in the brain. Biochim Biophys Acta 2005; 1746: 18-27
17 Gasparotto J, Ribeiro CT, Bortolin RC. et al. Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation. Sci Rep 2017; 7: 8795-8799
18 Guerrero E, Vasudevaraju P, Hegde ML. et al. Recent advances in α-synuclein functions, advanced glycation, and toxicity: implications for Parkinson’s disease. Mol Neurobiol 2013; 47: 525-536
19 Hald A, Lotharius J. Oxidative stress and inflammation in Parkinson’s disease: is there a causal link?. Exp Neurol 2005; 193: 279-290
20 Donato R, Sorci G, Rizzi F. et al. S100B’s double life: Intracellular regulator and extracellular signal. Biochim Biophys Acta - Mol Cell Res 2009; 1793: 1008-1022
21 Dukic-Stefanovic S, Gasic-Milenkovic J, Deuther-Conrad W. et al. Signal transduction pathways in mouse microglia N-11 cells activated by advanced glycation endproducts (AGEs). J Neurochem 2003; 87: 44-55
22 Halliday GM, Stevens CH. Glia: Initiators and progressors of pathology in Parkinson’s disease. Mov Disord 2011; 26: 6-17
23 Hreggvidsdóttir HS, Lundberg AM, Aveberger AC. et al. High mobility group box protein 1 (HMGB1)-partner molecule complexes enhance cytokine production by signaling through the partner molecule receptor. Mol Med 2012; 18: 224-230
24 Hudson BI, Carter AM, Harja E. et al. Identification, classification, and expression of RAGE gene splice variants. FASEB J 2008; 22: 1572-1580
25 Huttunen HJ, Fages C, Rauvala H. Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-kappaB require the cytoplasmic domain of the receptor but different downstream signaling pathways. J Biol Chem 1999; 274: 19919-19924
26 Huttunen HJ, Kuja-Panula J, Sorci G. et al. Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem 2000; 275: 40096-40105
27 Iannaccone S, Cerami C, Alessio M. et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord 2013; 19: 47-52
28 Kierdorf K, Fritz G. RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol 2013; 94: 55-68
29 Kim SJ, Ryu MJ, Han J. et al. Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation. Biochem Biophys Res Commun 2017; 493: 358-364
30 Michelle BL, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007; 8: 57-69
31 Alarcón R, Fuenzalida C, Santibáñez M. et al. Expression of scavenger receptors in glial cells. Comparing the adhesion of astrocytes and microglia from neonatal rats to surface-bound beta-amyloid. J Biol Chem 2005; 280: 30406-30415
32 Anzai Y, Hayashi M, Fueki N. et al. Protracted juvenile neuronal ceroid lipofuscinosis--an autopsy report and immunohistochemical analysis. Brain Dev 2006; 28: 462-465
33 Behl C, Davis JB, Lesley R. et al. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 1994; 77: 817-827
34 Berbaum K, Shanmugam K, Stuchbury G. et al. Induction of novel cytokines and chemokines by advanced glycation endproducts determined with a cytometric bead array. Cytokine 2008; 41: 198-203
35 Bierhaus A, Humpert PM, Morcos M. et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med 2005; 83: 876-886
36 Bigl K, Gaunitz F, Schmitt A. et al. Cytotoxicity of advanced glycation endproducts in human micro- and astroglial cell lines depends on the degree of protein glycation. J Neural Transm 2008; 115: 1545-1556
37 Loske C, Neumann A, Cunningham AM. et al. Cytotoxicity of advanced glycation endproducts is mediated by oxidative stress. J Neural Transm 1998; 105: 1005-1015
38 Wiedemann FR, Manfredi G, Mawrin C. et al. Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J Neurochem 2002; 80: 616-625
39 Loske C, Gerdemann A, Schepl W. et al. Transition metal-mediated glycoxidation accelerates cross-linking of β-amyloid peptide. Eur J Biochem 2000; 267: 4171-4178
40 Lotze MT, Tracey KJ. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 2005; 5: 331-342
41 Lovell MA, Robertson JD, Teesdale WJ. et al. Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 1998; 158: 47-52
42 Lue LF, Walker DG, Brachova L. et al. Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer’s disease: identification of a cellular activation mechanism. Exp Neurol 2001; 171: 29-45
43 Saletu B, Semlitsch H, Anderer P. et al. Psychophysiological research in psychiatry and neuropsychopharmacology. II. The investigation of antihypoxidotic/nootropic drugs (tenilsetam and co-dergocrine. Methods Find Exp Clin Pharmacol 1989; 11: 43-55
44 Stolzing A, Widmer R, Jung T. et al. Degradation of glycated bovine serum albumin in microglial cells. Free Radic Biol Med 2006; 40: 1017-1027
45 Sugaya K, Fukagawa T, Matsumoto KI. et al. Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 1994; 23: 408-419
46 Takeda A, Yasuda T, Miyata T. et al. Immunohistochemical study of advanced glycation end products in aging and Alzheimer’s disease brain. Neurosci Lett 1996; 221: 17-20
47 Takeuchi M, Kikuchi S, Sasaki N. et al. Involvement of advanced glycation end-products (AGEs) in Alzheimer’s disease. Curr Alzheimer Res 2004; 1: 39-46
48 Tan Y, Hong J, Doan T. et al. Presenilin-1 mutations associated with familial Alzheimer’s disease do not disrupt protein transport from the endoplasmic reticulum to the Golgi apparatus. Biochim Biophys Acta 1998; 1407: 69-78
49 Tanaka N, Yonekura H, Yamagishi SI. et al. The receptor for advanced glycation end products is induced by the glycation products themselves and tumor necrosis factor-alpha through nuclear factor-kappa B, and by 17beta-estradiol through Sp-1 in human vascular endothelial cells. J Biol Chem 2000; 275: 25781-25790
50 Casula M, Iyer AM, Spliet WGM. et al. Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue. Neuroscience 2011; 179: 233-243
51 Thomas M, Baynes J, Thorpe S. et al. The role of AGEs and AGE inhibitors in diabetic cardiovascular disease. Curr Drug Targets 2005; 6: 453-474
52 Choi YG, Lim S. Nε-(carboxymethyl)lysine linkage to α-synuclein and involvement of advanced glycation end products in α-synuclein deposits in an MPTP-intoxicated mouse model. Biochimie 2010; 92: 1379-1386
53 Dalfó E, Portero-Otín M, Ayala V. et al. Evidence of oxidative stress in the neocortex in incidental Lewy body disease. J Neuropathol Exp Neurol 2005; 64: 816-830
54 Obrenovich ME, Monnier VM. Glycation stimulates amyloid formation. Sci aging Knowl Environ 2004; 2004: 3-9
55 Wong A, Lüth HJ, Deuther-Conrad W. et al. Advanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer’s disease. Brain Res 2001; 920: 32-40
56 Thornalley PJ. Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts. Arch Biochem Biophys 2003; 419: 31-40
57 Ashraf JM, Ahmad S, Choi I. et al. Recent advances in detection of AGEs: Immunochemical, bioanalytical and biochemical approaches. IUBMB life 2015; 67: 897-913