scholarly journals HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2/PP2A/AKT1/GSK3 for Schizophrenia Risk

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 145
Author(s):  
Qiujin Yan ◽  
Xiulin Wu ◽  
Ping Zhou ◽  
Yan Zhou ◽  
Xuhang Li ◽  
...  

An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of schizophrenia. The dopamine (DA) hypothesis is the cornerstone in research and clinical practice related to schizophrenia. Here, we found that the concentration of DA and the expression of DA receptor D2 (DRD2) were significantly higher in schizophrenia patients than in healthy individuals. Intriguingly, there was a positive correlation between HERV-W ENV and DA concentration. Depth analyses showed that there was a marked consistency between HERV-W ENV and DRD2 in schizophrenia. Studies in vitro indicated that HERV-W ENV could increase the DA concentration by regulating DA metabolism and induce the expression of DRD2. Co-IP assays and laser confocal scanning microscopy indicated cellular colocalization and a direct interaction between DRD2 and HERV-W ENV. Additionally, HERV-W ENV caused structural and functional abnormalities of DA neurons. Further studies showed that HERV-W ENV could trigger the PP2A/AKT1/GSK3 pathway via DRD2. A whole-cell patch-clamp analysis suggested that HERV-W ENV enhanced sodium influx through DRD2. In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia.

2010 ◽  
Vol 26 (8) ◽  
pp. 883-888 ◽  
Author(s):  
Ute Gabriel ◽  
Annette Steidler ◽  
Lutz Trojan ◽  
Maurice Stephan Michel ◽  
Wolfgang Seifarth ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 192 ◽  
Author(s):  
Guangsheng Cai ◽  
Simiao Wang ◽  
Lang Zhao ◽  
Yating Sun ◽  
Dongsheng Yang ◽  
...  

A series of thiophene derivatives (TPs) were synthesized and evaluated for cytotoxicity in HepG2 and SMMC-7721 cell lines by MTT assay. TP 5 was identified as a potential anticancer agent based on its ability to inhibit tumor cell growth. Drawbacks of TPs, including poor solubility and high toxicity, were overcome through delivery using self-assembling HSA nanoparticles (NPs). The optimum conditions for TP 5-NPs synthesis obtained by adjusting the temperature and concentration of TP 5. The NPs had an encapsulation efficiency of 99.59% and drug-loading capacity of 3.70%. TP 5 was slowly released from TP 5-NPs in vitro over 120 h. HepG2 and SMMC-7721 cell lines were employed to study cytotoxicity of TP 5-NPs, which exhibited high potency. ROS levels were elevated and mitochondrial membrane potentials reversed when the two cell lines were treated with TP 5-NPs for 12 h. Cellular uptake of fluorescence-labeled TP 5-NPs in vitro was analyzed by flow cytometry and laser confocal scanning microscopy. Fluorescence intensity increased over time, suggesting that TP 5-NPs were efficiently taken up by tumor cells. In conclusion, TP 5-NPs showed great promise as an anticancer therapeutic agent.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Can Kuskonmaz ◽  
Alberto De Stefani ◽  
Gilberto Artioli ◽  
Matteo Zanarini ◽  
Giulio Alessandri Bonetti ◽  
...  

2007 ◽  
Vol 353-358 ◽  
pp. 874-877
Author(s):  
Hai Yang Yu ◽  
Shan Shan Gao ◽  
Zhen Bing Cai ◽  
Min Wang ◽  
Xin Min Chen ◽  
...  

Under imitating human physiological solution, the fretting behaviors of flat cortical bone specimen from fresh human femur in the axial orientation against TA2 titanium ball with diameter of 40 mm had been investigated. The coefficients of friction (COF) and fretting logs were calculated automatically. The worn surfaces of the cortical bone were analyzed by means of laser confocal scanning microscopy. The results showed that the fretting logs for the cortical bone varied with the increase of the cycles from the elastic partial slip (D=5 (m), the elastoplastic partial slip (D=15 (m) to gross slip (D=30 (m), respectively. The fretting regime transformed from the partial slip regime directly to the gross slip regime without the mixed fretting regime. And the evolution of the COF in each fretting condition was also compared statistically. The fretting damage in the elastic partial slip state was slight. But the abrasive wear and micro-fracture were observed in the plastoelastic partial slip state and gross slip regime. The wear depth increased with cycles and well related to the COF of the cortical bone in each fretting condition. To reduce the fretting damages of bone, it is advisable to control the displacement amplitude at bone-implant interface.


2021 ◽  
Vol 11 ◽  
Author(s):  
Eoin Dervan ◽  
Dibyangana D. Bhattacharyya ◽  
Jake D. McAuliffe ◽  
Faizan H. Khan ◽  
Sharon A. Glynn

Human endogenous retroviruses (HERV), ancient integrations of exogenous viruses, make up 8% of our genome. Long thought of as mere vestigial genetic elements, evidence is now accumulating to suggest a potential functional role in numerous pathologies including neurodegenerative diseases, autoimmune disorders, and multiple cancers. The youngest member of this group of transposable elements is HERV-K (HML-2). Like the majority of HERV sequences, significant post-insertional mutations have disarmed HERV-K (HML-2), preventing it from producing infectious viral particles. However, some insertions have retained limited coding capacity, and complete open reading frames for all its constituent proteins can be found throughout the genome. For this reason HERV-K (HML-2) has garnered more attention than its peers. The tight epigenetic control thought to suppress expression in healthy tissue is lost during carcinogenesis. Upregulation of HERV-K (HML-2) derived mRNA and protein has been reported in a variety of solid and liquid tumour types, and while causality has yet to be established, progressively more data are emerging to suggest this phenomenon may contribute to tumour growth and metastatic capacity. Herein we discuss its potential utility as a diagnostic tool and therapeutic target in light of the current in vitro, in vivo and clinical evidence linking HERV-K (HML-2) to tumour progression.


2012 ◽  
Vol 457-458 ◽  
pp. 525-530
Author(s):  
Takashi Honda ◽  
Edson Costa Santos ◽  
Katsuyuki Kida ◽  
Takuya Shibukawa

In this work, a 5 mm diameter 13Cr-2Ni-2Mo stainless steel shaft was quenched by induction heating by using a 15 mm diameter coil and the influence of the induction heating process on the material’s microstructure and mechanical properties was investigated by laser confocal scanning microscopy, X-ray diffraction (XRD) and Vickers hardness testing. Through the heat treatment process, the hardness increased two-fold and the XRD pattern changed indicating occurrence of martensitic transformation. Based on these results, it is concluded that induction heating can be used as a quick method of hardening 13Cr-2Ni-2Mo alloy steel.


Placenta ◽  
2016 ◽  
Vol 46 ◽  
pp. 106
Author(s):  
Kazuki Morita ◽  
Takeshi Nagamatsu ◽  
So Nakagawa ◽  
Jun Sugimoto ◽  
Kei Kawana ◽  
...  

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Oliver Acton ◽  
Tim Grant ◽  
Giuseppe Nicastro ◽  
Neil J. Ball ◽  
David C. Goldstone ◽  
...  

AbstractThe HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old. Many maintain intact open reading frames and provirus expression together with HML2 particle formation are observed in early stage human embryo development and are associated with pluripotency as well as inflammatory disease, cancers and HIV-1 infection. Here, we reconstruct the core structural protein (CA) of an HML2 retrovirus, assemble particles in vitro and employ single particle cryogenic electron microscopy (cryo-EM) to determine structures of four classes of CA Fullerene shell assemblies. These icosahedral and capsular assemblies reveal at high-resolution the molecular interactions that allow CA to form both pentamers and hexamers and show how invariant pentamers and structurally plastic hexamers associate to form the unique polyhedral structures found in retroviral cores.


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