Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: the Receptor for Advanced Glycation End Products (RAGE)

Kong, Yanyan; Wang, Fushuai; Wang, Jiao; Liu, Cuiping; Zhou, Yinping; Xu, Zhonghui; Zhang, Chencheng; Sun, Bomin; Guan, Yihui

doi:10.3389/fnagi.2020.00217

Cited by 50 publications

(41 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…RAGE is a 35 kDa protein in the immunoglobulin superfamily, and its increased expression can lead to in ammatory conditions [23,32]. In the case of asthma, the close relationship between RAGE overexpression and asthma development has been reported previously by ourselves and others [22,23,33,34]. In the present study, we observed that RAGE is up-regulated in PBMCs from asthma patients, which was consistent with its previously reported expression pattern [22].…”

Section: Discussionsupporting

confidence: 92%

miR-3934 suppresses basophil apoptosis and secretion of inflammatory cytokines by targeting RAGE in asthma

Han

Dou

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background Several miRNAs are now known to have clear connections to the pathogenesis of asthma. The present study focused on the potential role of miR-3934 during asthma development. Methods The basophils was isolated from 50 asthmatic patients and 50 health controls. The expression level of miR-3934 was examined by RT-qPCR and the expression of receptor for advanced glycation end products (RAGE) was detected by western blot. In addition, the analysis of apoptotic basophils was performed by flow cytometry; the expression level of inflammatory cytokines was detected by ELISA kits; and several important proteins in TGF-β/Smad signaling were examined by western blot. Results miR-3934 was down-regulated in the basophils of asthmatic patients. The expression of the pro-inflammatory cytokines IL-6, IL-8 and IL-33 was enhanced in basophils from asthmatic patients, and this effect was partially reversed by transfection of miR-3934 mimics. Furthermore, receiver operating characteristics analysis showed that miR-3934 levels can be used to distinguish asthma patients from healthy individuals. miR-3934 partially inhibited advanced glycation end products-induced increases in basophil apoptosis by suppressing expression of RAGE. Conclusion Our results indicate that miR-3934 acts to mitigate the pathogenesis of asthma by targeting RAGE and suppressing TGF-β/Smad signaling.

show abstract

Section: Discussionsupporting

confidence: 92%

miR-3934 suppresses basophil apoptosis and secretion of inflammatory cytokines by targeting RAGE in asthma

Han

Dou

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…There is evidence showing that AGEs specific receptors (RAGEs), which are found in neurons, microglia, astrocytes, and vascular endothelial cells, interacts not only with AGEs, but also with Aβ and mediate inflammatory effects [ 309 ]; it is even described that RAGEs could mediate Aβ transport through blood brain barrier (BBB) or enhance expression of BACE1, thus promoting Aβ formation [ 310 ]. It has been proved that AGEs could induce tau hyperphosphorylation through RAGEs-GSK3β signaling activation [ 311 ], and direct AGEs injection in mice brain displayed AD pathological features, such as decreased memory and increased tau phosphorylation, APP expression, and Aβ 42 formation [ 312 , 313 ].…”

Section: The Relation Between T2dm and Ad: A Molecular Approachmentioning

confidence: 99%

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Burillo

Marqués

Jiménez

et al. 2021

Cells

View full text Add to dashboard Cite

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

show abstract

“…The long-live proteins are preferentially modified to form AGEs and the high stability of Aβ makes it an ideal substrate for non-enzymatic glycation and formation of AGEs. A role of blood sugars would also explain the link observed between the apparently unrelated diabetes and AD; diabetic patients have a 2-5-fold higher tendency to develop AD compared with nondiabetic individuals [ 54 , 55 , 56 , 57 , 58 ].…”

Section: Glycation Role In Amyloid Aggregationmentioning

confidence: 99%

Understanding the Role of Protein Glycation in the Amyloid Aggregation Process

Sirangelo

2021

IJMS

View full text Add to dashboard Cite

Protein function and flexibility is directly related to the native distribution of its structural elements and any alteration in protein architecture leads to several abnormalities and accumulation of misfolded proteins. This phenomenon is associated with a range of increasingly common human disorders, including Alzheimer and Parkinson diseases, type II diabetes, and a number of systemic amyloidosis characterized by the accumulation of amyloid aggregates both in the extracellular space of tissues and as intracellular deposits. Post-translational modifications are known to have an active role in the in vivo amyloid aggregation as able to affect protein structure and dynamics. Among them, a key role seems to be played by non-enzymatic glycation, the most unwanted irreversible modification of the protein structure, which strongly affects long-living proteins throughout the body. This study provided an overview of the molecular effects induced by glycation on the amyloid aggregation process of several protein models associated with misfolding diseases. In particular, we analyzed the role of glycation on protein folding, kinetics of amyloid formation, and amyloid cytotoxicity in order to shed light on the role of this post-translational modification in the in vivo amyloid aggregation process.

show abstract

Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: the Receptor for Advanced Glycation End Products (RAGE)

Cited by 50 publications

References 66 publications

miR-3934 suppresses basophil apoptosis and secretion of inflammatory cytokines by targeting RAGE in asthma

miR-3934 suppresses basophil apoptosis and secretion of inflammatory cytokines by targeting RAGE in asthma

Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Understanding the Role of Protein Glycation in the Amyloid Aggregation Process

Contact Info

Product

Resources

About