scholarly journals Chaperone Sigma1R and Antidepressant Effect

2020 ◽  
Vol 21 (19) ◽  
pp. 7088
Author(s):  
Mikhail V. Voronin ◽  
Yulia V. Vakhitova ◽  
Sergei B. Seredenin
Keyword(s):  
Endoplasmic Reticulum ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Scientific Literature ◽  
Unique Property ◽  
Antidepressant Effect ◽  
Ligand Activation ◽  
Current Review ◽  
Intracellular Translocation

This review analyzes the current scientific literature on the role of the Sigma1R chaperone in the pathogenesis of depressive disorders and pharmacodynamics of antidepressants. As a result of ligand activation, Sigma1R is capable of intracellular translocation from the endoplasmic reticulum (ER) into the region of nuclear and cellular membranes, where it interacts with resident proteins. This unique property of Sigma1R provides regulation of various receptors, ion channels, enzymes, and transcriptional factors. The current review demonstrates the contribution of the Sigma1R chaperone to the regulation of molecular mechanisms involved in the antidepressant effect.

scholarly journals Nox4 Mediates RANKL-induced ER-Phagy and Osteoclastogenesis via Activating ROS/PERK/eIF-2α/ATF4 Pathway

2020 ◽  
Author(s):  
Jing Sun ◽  
wugui chen ◽  
Songtao Li ◽  
Sizhen Yang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Bone Resorption ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Protein Levels ◽  
Unfolded Protein ◽  
Regulatory Effects ◽  
Protein Response

Abstract Background: Receptor activator of nuclear factor-κB ligand (RANKL) has been found to induce osteoclastogenesis and bone resorption. However, the underlying molecular mechanisms remain unclear. Methods: Osteoclastogenesis was evaluated by number of TRAP-positive multinuclear (≥3) osteoclasts, bone resorption pits and expression levels of related genes. Autophagy activity were evaluated by LC3-II/LC3-I ratio, number of autophagic vacuoles and adenovirus-mRFP-GFP-tagged LC3 reporting system; Inhibitor chloroquine (CQ) was used to verified the role of autophagy in RANKL-induced osteoclastogenesis; Via downregulating Nox4 with inhibitor (DPI) and retrovirus-conveyed shRNA, we further explored the importance of Nox4 in RANKL-induced autophagy and osteoclastogenesis, as well as the regulatory effects of Nox4 on nonmitochondrial reactive oxygen species (ROS) and PERK/eIF-2α/ATF4 pathway. Intracellular ROS scavenger (NAC), mitochondrial-targeted antioxidant (MitoTEMPO) and inhibitor of PERK (GSK2606414) were also employed to investigate the role of ROS and PERK/eIF-2α/ATF4 pathway in RANKL-induced autophagy and osteoclastogenesis. Results: RANKL markedly increased autophagy, while CQ treatment caused reduction of RANKL-induced autophagy and osteoclastogenesis. Consistent with the increased autophagy, the protein levels of Nox4 were significantly increased, and Nox4 was selectively localized within the endoplasmic reticulum (ER) after RANKL stimulation. DPI and shRNA efficiently decreased the protein level and (or) activity of Nox4 in the ER and inhibited RANKL-induced autophagy and osteoclastogenesis. Mechanistically, we found that Nox4 regulates RANKL-induced autophagy activation and osteoclastogenesis by stimulating the production of nonmitochondrial ROS. Additionally, Nox4-derived nonmitochondrial ROS dramatically activate PERK/eIF-2α/ATF4, which is a critical unfolded protein response (UPR)-related signaling pathway during ER stress. Blocking the activation of the PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS antioxidant or PERK inhibitor (GSK2606414) treatment significantly inhibited endoplasmic reticulum autophagy (ER-phagy) during RANKL-induced osteoclastogenesis. Conclusions: Our findings provide new insights into the processes of RANKL-induced osteoclastogenesis and will help the development of new therapeutic strategies for osteoclastogenesis-related diseases.

scholarly journals Don’t Believe What You See in Mouth, Listen To Condyles - A Systemic Review

2014 ◽  
Vol 1 (2) ◽  
pp. 22
Author(s):  
Adil . ◽  
Anisha Vallakati ◽  
Ankur Aggarwal ◽  
H. Jyothikiran ◽  
S. Ravi
Keyword(s):  
Quality Of Life ◽  
Scientific Literature ◽  
Systemic Review ◽  
Interdisciplinary Teamwork ◽  
Current Review ◽  
Centric Relation ◽  
Conservative Dentistry ◽  
Centric Occlusion

Centric relation, static and dynamic occlusion are less talked about than its actual importance in dentistry. Their relevance to different disciplines of odontology (general dentistry, conservative dentistry, orthodontics, prosthodontics, dental technicians) has been well documented. Numerous articles in scientific literature regarding the importance and necessity of interdisciplinary teamwork in dentistry to correct problems associated with occlusion has been documented. The centric occlusion and centric relation (CO CR) discrepancy is multifactorial with a degree of psychogenic influence varying throughout an individual's life with phases of symptoms affecting the quality of life. The current review highlights role of various disciplines in rectifying problems relating to discrepancy in centric occlusion and centric relation.

scholarly journals The NMDA receptor and new possibilities in antidepressant therapy

2018 ◽  
Vol 72 ◽  
pp. 788-794
Author(s):  
Weronika Stasiuk ◽  
Monika Prendecka ◽  
Krzysztof Chara ◽  
Teresa Małecka-Massalska
Keyword(s):  
Nmda Receptor ◽  
Affective Disorders ◽  
Depressive Disorders ◽  
Treatment Strategies ◽  
Antidepressant Effect ◽  
Antidepressant Medications ◽  
Treatment Of Depression ◽  
Potential Alternative ◽  
Disorder Treatment

Due to the inadequate effectiveness of pharmacological methods currently being utilized in the treatment of depression, there is an ongoing need to find newer and safer treatment strategies. Studies undertaken to date aimed at finding more effective methods for the treatment of affective disorders have been widened to incorporate other neurotransmission systems. Experiments with compounds that modify the function of the glutamatergic system highlight a new direction in the study of affective disorder treatment methods. It has been shown that one of the key mechanisms in achieving an antidepressant effect is by weakening the function of the NMDA receptor. Pre-clinical as well as clinical trials have revealed that compounds that modulate the activity of the NMDA receptor are characterized by a significant antidepressant effect which identifies them as potential antidepressant medications. In this study an attempt was made at identifying the role of the NMDA receptor in the pathogenesis and therapy of depressive disorders as well as the influence of ligands (especially antagonist) of this receptor on the function of classical antidepressant medications. Results shown in the attached studies by numerous scientists will in the future potentially add to the development of more effective and safer therapies for patients with affective disorders as well as offering a potential alternative in the treatment of drug resistant forms of depression.

Endoplasmic reticulum quality control and dysmyelination

2011 ◽  
Vol 2 (4) ◽  
pp. 261-274 ◽  
Author(s):  
Allison Kraus ◽  
Marek Michalak
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Molecular Mechanisms ◽  
Review Paper ◽  
Cholesterol Biosynthesis ◽  
Charcot Marie Tooth ◽  
Myelin Sheaths ◽  
Conduction Velocities ◽  
Endoplasmic Reticulum Quality Control

AbstractDysmyelination contributes to several human diseases including multiple sclerosis, Charcot-Marie-Tooth, leukodystrophies, and schizophrenia and can result in serious neurological disability. Properly formed, compacted myelin sheaths are required for appropriate nerve conduction velocities and the health and survival of neurons. Many different molecular mechanisms contribute to dysmyelination and many of these mechanisms originate at the level of the endoplasmic reticulum. The endoplasmic reticulum is a critical organelle for myelin biosynthesis and maintenance as the site of myelin protein folding quality control, Ca2+ homeostasis, cholesterol biosynthesis, and modulation of cellular stress. This review paper highlights the role of the endoplasmic reticulum and its resident molecules as an upstream and dynamic contributor to myelin and myelin pathologies.

scholarly journals Gm12664-201, A Pseudogene-Transcribed RNA Promotestriglyceride Accumulation Via Activating Endoplasmic Reticulum Stress Pathway in Hepatocytes

2021 ◽  
Author(s):  
Yanhe Zhao ◽  
Zhen Tian ◽  
Yubing Jia ◽  
Dan Shi ◽  
Xinyue Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Molecular Mechanisms ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Qrt Pcr ◽  
Triglyceride Accumulation ◽  
Stress Pathway

Abstract Background: Typical pseudogenes expressions have been reported to been associated with liver diseases. However, whether pseudogenes contribute to non-alcoholic fatty liver disease (NAFLD) and triglyceride (TG) accumulation and the underlying molecular mechanisms are poorly understood. We aimed to elucidate the role of Gm12664-201 in TG accumulation and the potential mechanism.Method and Results: We identified Gm12664-01 in high-fat diet (HFD) fed mice using microarray and confirmed its expression in both vivo and vitro high fat models with quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then changed the level of Gm12664-201 in vitro to determine the role of it in TG accumulation, which evaluated by Oil red O staining and enzymatic method. The underlying mechanisms of Gm12664-01 in TG accumulation were investigated by detecting signaling markers BiP, PERK, ATF6, CHOP, eIF2α, XBP1 and ATF4 with qRT-PCR and western blotting. We found that Gm12664-201 was markedly increased in liver tissue of HFD mice and steric acid (SA) incubated AML-12 cells. Gm12664-201 overexpression rendered AML-12 cells susceptible to triglyceride (TG) accumulation, and silencing pseudogene Gm12664-201 expression efficiently alleviated SA-induced TG accumulation. Further studies revealed that Gm12664-201 regulates endoplasmic reticulum stress signaling markers BiP, PERK, ATF6, CHOP, eIF2α, XBP1 and ATF4 expression, which may be responsible for increased TG accumulation in hepatocytes.Conclusions: Upregulation of pseudogene Gm12664-201 induced by HFD promotes triglyceride accumulation and activates ER stress pathway in hepatocytes.

scholarly journals The Role of Omics Approaches to Characterize Molecular Mechanisms of Rare Ovarian Cancers: Recent Advances and Future Perspectives

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1481
Author(s):  
Yashwanth Subbannayya ◽  
Riccardo Di Fiore ◽  
Silvana Anna Maria Urru ◽  
Jean Calleja-Agius
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Delayed Diagnosis ◽  
Cancer Recurrence ◽  
Potential Candidate ◽  
Ovarian Cancers ◽  
Current Review ◽  
Mechanisms Of Carcinogenesis ◽  
Underlying Mechanisms

Rare ovarian cancers are ovarian cancers with an annual incidence of less than 6 cases per 100,000 women. They generally have a poor prognosis due to being delayed diagnosis and treatment. Exploration of molecular mechanisms in these cancers has been challenging due to their rarity and research efforts being fragmented across the world. Omics approaches can provide detailed molecular snapshots of the underlying mechanisms of these cancers. Omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, can identify potential candidate biomarkers for diagnosis, prognosis, and screening of rare gynecological cancers and can aid in identifying therapeutic targets. The integration of multiple omics techniques using approaches such as proteogenomics can provide a detailed understanding of the molecular mechanisms of carcinogenesis and cancer progression. Further, omics approaches can provide clues towards developing immunotherapies, cancer recurrence, and drug resistance in tumors; and form a platform for personalized medicine. The current review focuses on the application of omics approaches and integrative biology to gain a better understanding of rare ovarian cancers.

scholarly journals The Expanding Role of Ketogenic Diets in Adult Neurological Disorders

2018 ◽  
Vol 8 (8) ◽  
pp. 148 ◽  
Author(s):  
Tanya McDonald ◽  
Mackenzie Cervenka
Keyword(s):  
Alzheimer’S Disease ◽  
Adverse Effects ◽  
Malignant Glioma ◽  
Ketogenic Diet ◽  
Neurological Disorders ◽  
Scientific Literature ◽  
Management Strategies ◽  
Ketogenic Diets ◽  
Current Review

The current review highlights the evidence supporting the use of ketogenic diet therapies in the management of adult epilepsy, adult malignant glioma and Alzheimer’s disease. An overview of the scientific literature, both preclinical and clinical, in each area is presented and management strategies for addressing adverse effects and compliance are discussed.

scholarly journals Endoplasmic Reticulum Stress and Diabetic Cardiomyopathy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Jiancheng Xu ◽  
Qi Zhou ◽  
Wei Xu ◽  
Lu Cai
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Lipid Synthesis ◽  
The Unfolded Protein Response ◽  
Cell Stress Response

The endoplasmic reticulum (ER) is an organelle entrusted with lipid synthesis, calcium homeostasis, protein folding, and maturation. Perturbation of ER-associated functions results in an evolutionarily conserved cell stress response, the unfolded protein response (UPR) that is also called ER stress. ER stress is aimed initially at compensating for damage but can eventually trigger cell death if ER stress is excessive or prolonged. Now the ER stress has been associated with numerous diseases. For instance, our recent studies have demonstrated the important role of ER stress in diabetes-induced cardiac cell death. It is known that apoptosis has been considered to play a critical role in diabetic cardiomyopathy. Therefore, this paper will summarize the information from the literature and our own studies to focus on the pathological role of ER stress in the development of diabetic cardiomyopathy. Improved understanding of the molecular mechanisms underlying UPR activation and ER-initiated apoptosis in diabetic cardiomyopathy will provide us with new targets for drug discovery and therapeutic intervention.

scholarly journals Nox4 mediates RANKL-induced ER-phagy and Osteoclastogenesis via activating ROS/PERK/eIF-2α/ATF4 Pathway

2021 ◽  
Author(s):  
Jing Sun ◽  
Wugui Cheng ◽  
Songtao Li ◽  
Sizhen Yang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Protein Levels ◽  
Unfolded Protein ◽  
Ros Scavenger ◽  
Regulatory Effects ◽  
Protein Response

Abstract Background: Receptor activator of nuclear factor-κB ligand (RANKL) has been found to induce osteoclastogenesis and bone resorption. However, the underlying molecular mechanisms remain unclear. Results: Inhibitor chloroquine (CQ) was used to verified the role of autophagy in RANKL-induced osteoclastogenesis; Via downregulating Nox4 with inhibitor (DPI) and retrovirus-conveyed shRNA, we further explored the importance of Nox4 in RANKL-induced autophagy and osteoclastogenesis, as well as the regulatory effects of Nox4 on nonmitochondrial reactive oxygen species (ROS) and PERK/eIF-2α/ATF4 pathway.Intracellular ROS scavenger (NAC), mitochondrial-targeted antioxidant (Mito-TEMPO) and inhibitor of PERK (GSK2606414) were also employed to investigate the role of ROS and PERK/eIF-2α/ATF4 pathway in RANKL-induced autophagy and osteoclastogenesis. RANKL markedly increased autophagy, while CQ treatment caused reduction of RANKL-induced autophagy and osteoclastogenesis. Consistent with the increased autophagy, the protein levels of Nox4 were significantly increased, and Nox4 was selectively localized within the endoplasmic reticulum (ER) after RANKL stimulation. DPI and shRNA efficiently decreased the protein level and (or) activity of Nox4 in the ER and inhibited RANKL-induced autophagy and osteoclastogenesis. Mechanistically, we found that Nox4 regulates RANKL-induced autophagy activation by stimulating the production of nonmitochondrial ROS. Additionally, Nox4-derived nonmitochondrial ROS dramatically activate PERK/eIF-2α/ATF4, which is a critical unfolded protein response (UPR)-related signaling pathway. Blocking the activation of the PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS antioxidant or PERK inhibitor (GSK2606414) treatment significantly inhibited endoplasmic reticulum autophagy (ER-phagy) during RANKL-induced osteoclastogenesis. Conclusions: Our findings provide new insights into the processes of RANKL-induced osteoclastogenesis and will help the development of new therapeutic strategies for osteoclastogenesis-related diseases.

scholarly journals Osteogenic Differentiation of Mesenchymal Stem Cells via Curcumin-Containing Nanoscaffolds

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Khadijeh Khezri ◽  
Solmaz Maleki Dizaj ◽  
Yalda Rahbar Saadat ◽  
Simin Sharifi ◽  
Shahriar Shahi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Structural Modifications ◽  
Current Review ◽  
Great Body ◽  
Health Related ◽  
The Impact

The diverse pleiotropic pharmacological effects of curcumin nanoformulations have turned it into an attractive natural compound in different health-related problems. A great body of evidence has shown the impact of curcumin and its nanoformulations on the differentiation of stem cells. The current review highlights cellular and molecular mechanisms connected with the osteogenic differentiation of mesenchymal stem cells (MSCs) in the scaffolds benefiting from the presence of nanocurcumin pointing toward the role of inhibitory or stimulant signal transduction pathways in detail. Moreover, the effects of different concentrations as well as the structural modifications of curcumin on the differentiation of MSCs have been addressed.

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