Caveolin-1: A promising therapeutic target for diverse diseases

2021 ◽  
Vol 14 ◽  
Author(s):  
Shivani Gokani ◽  
Lokesh Kumar Bhatt
Keyword(s):  
Viral Entry ◽  
Therapeutic Target ◽  
Hippocampal Neurons ◽  
Physiological Role ◽  
Clinical Applications ◽  
Caveolin 1 ◽  
Patients With Cancer ◽  
Cellular Events ◽  
Promising Therapeutic Target

: The plasma membrane of eukaryotic cells contains small flask-shaped invaginations known as caveolae that are involved in the regulation of cellular signaling. Caveolin-1 is a 21-24kDa protein localized in the caveolar membrane. Caveolin-1 (Cav-1) has been considered as a master regulator among the various signaling molecules. It has been emerging as a chief protein regulating cellular events associated with homeostasis, caveolae formation, and caveolae trafficking. In addition to the physiological role of cav-1, it has a complex role in the progression of various diseases. Caveolin-1 has been identified as a prognosticator in patients with cancer and has a dual role in tumorigenesis. The expression of Cav-1 in hippocampal neurons and synapses is related to neurodegeneration, cognitive decline, and aging. Despite the ubiquitous association of caveolin-1 in various pathological processes, the mechanisms associated with these events are still unclear. Caveolin-1 has a significant role in various events of the viral cycle, such as viral entry. This review will summarize the role of cav-1 in the development of cancer, neurodegeneration, glaucoma, cardiovascular diseases, and infectious diseases. The therapeutic perspectives involving clinical applications of Caveolin-1 have also been discussed. The understanding of the involvement of caveolin-1 in various diseased states provides insights into how it can be explored as a novel therapeutic target.

scholarly journals The Role of F11R in Pancreatic Cancer Malignancy and Its Clinical Implication as a Therapeutic Target

2019 ◽  
Author(s):  
Haidi zhang ◽  
Chunyan Zhao ◽  
Xianhua Hu ◽  
Shuai He ◽  
Jinchuan Yu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Target ◽  
Immunoglobulin Superfamily ◽  
Experimental Conditions ◽  
Cycle Arrest ◽  
Pancreatic Cancer Cells ◽  
Promising Therapeutic Target ◽  
Cell Invasiveness

Abstract Abstract Background The F11 receptor belongs to the immunoglobulin superfamily and is expressed in epithelial and endothelial cells. F11R mediates the formation of tight junctions between the epithelium and endothelium, and participates in the invasion and metastasis of tumor cells. We have previously shown that the F11R gene is closely related to KRas (P= 0.76), a known therapeutic target for pancreatic cancer (PCa). In recent years, it has been found that F11R is expressed in different tumors and has biological effects.However, according to different tumor cases, different cell lines and experimental conditions, the regulatory results and mechanisms of F11R on tumor are different, even contradictory,and the expression, clinical significance and biological mechanism of F11R in tumor tissues have not been reported in detail. Results To investigate the role of F11R in carcinogenesis of PCa and the potential of F11R as a therapies target for PCa, we silenced F11R (-/-) in the PCa cell line PANC-1 (known to express high levels of KRas) using lentiviral approaches.We found that F11R silencing led to decreased cell proliferation, a loss of cell invasiveness, reduced colony forming ability, cell cycle arrest in G1 phase, cells apoptosis enhanced, and ros enhanced. In vitro data showed that inhibition of F11R decreased proliferation and invasiveness of cancer cells.The present results suggest that F11R may be a promising therapeutic target for PCa. Conclusions This study used bioinformatics combined with gene chip data to find the gene F11R, which is closely related to KRAS gene, and we used lentivirus to package shRNA plasmid to interfere with the gene F11R in pancreatic cancer panc-1 cells. A series of biobehavioral studies indicated the biobehavioral function and malignancy of panc-1 in pancreatic cancer cells with negative regulation of F11R gene.Based on this, we need to continue to clarify the expression of F11R gene in clinical case samples to determine whether F11R gene can be a new therapeutic target for pancreatic cancer.

Vitamin D/VDR in acute kidney injury: a potential therapeutic target

2020 ◽  
Vol 27 ◽  
Author(s):  
Siqing Jiang ◽  
Lihua Huang ◽  
Wei Zhang ◽  
Hao Zhang
Keyword(s):  
Vitamin D ◽  
Acute Kidney Injury ◽  
Therapeutic Target ◽  
Poor Prognosis ◽  
Therapeutic Potential ◽  
Kidney Injury ◽  
Potential Therapeutic Target ◽  
Promising Therapeutic Target ◽  
Incidence And Mortality

: Despite many strategies and parameters used in clinical practice, the incidence and mortality of acute kidney injury (AKI) are still high with poor prognosis. With the development of molecular biology, the role of vitamin D and vitamin D receptor (VDR) in AKI is drawing increasing attention. Accumulated researches have suggested that Vitamin D deficiency is a risk factor of both clinical and experimental AKI, and vitamin D/VDR could be a promising therapeutic target against AKI. However, more qualitative clinical researches are needed to provide stronger evidence for clinical application of vitamin D and VDR agonists in the future. Issues like the route and dosage of administration also await more attention. The present review aims to summarize the current works on the role of vitamin D/VDR in AKI and try to provide some new insight of its therapeutic potential.

The Role of ASIC1a in Epilepsy: A Potential Therapeutic Target

2021 ◽  
Vol 19 ◽  
Author(s):  
Yu Cheng ◽  
Wuqiong Zhang ◽  
Yue Li ◽  
Ting Jiang ◽  
Buhajar Mamat ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Brain Diseases ◽  
Mammalian Brain ◽  
Acid Sensing Ion Channels ◽  
Promising Therapeutic Target ◽  
Pathological Mechanism ◽  
Tissue Acidosis ◽  
Epileptogenic Foci

Background: Epilepsy represents one of the most common brain diseases among humans. Tissue acidosis is a common phenomenon in epileptogenic foci. This said, its roles in epileptogenesis remain unclear. Acid-sensing ion channel-1a (ASIC1a) represents a potential way to assess new therapies. ASIC1a, mainly expressed in the mammalian brain, is a type of protein-gated cation channel. It has been shown to play an important role in the pathological mechanism of various diseases, including stroke, epilepsy, and multiple sclerosis. Methods: Data were collected from Web of Science, Medline, PubMed, through searching for these keywords: "Acid-sensing ion channels 1a" or "ASIC1a" and "epilepsy" or "seizure". Results: The role of ASIC1a in epilepsy remains controversial; it may represent a promising therapeutic target of epilepsy. Conclusion:This review is intended to provide an overview of the structure, trafficking, and molecular mechanisms of ASIC1a in order to further elucidate the role of ASIC1a in epilepsy.

scholarly journals The Role of Cardiokines in Heart Diseases: Beneficial or Detrimental?

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Ye-Shun Wu ◽  
Bin Zhu ◽  
Ai-Lin Luo ◽  
Ling Yang ◽  
Chun Yang
Keyword(s):  
Cardiovascular Disease ◽  
Heart Disease ◽  
Disease Burden ◽  
Heart Diseases ◽  
Critical Role ◽  
Physiological Role ◽  
Myocardial Damage ◽  
Promising Therapeutic Target ◽  
Potential Therapeutics

Cardiovascular disease remains the leading cause of morbidity and mortality, imposing a major disease burden worldwide. Therefore, there is an urgent need to identify new therapeutic targets. Recently, the concept that the heart acts as a secretory organ has attracted increasing attention. Proteins secreted by the heart are called cardiokines, and they play a critical physiological role in maintaining heart homeostasis or responding to myocardial damage and thereby influence the development of heart diseases. Given the critical role of cardiokines in heart disease, they might represent a promising therapeutic target. This review will focus on several cardiokines and discuss their roles in the pathogenesis of heart diseases and as potential therapeutics.

scholarly journals TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 241
Author(s):  
Flaviana Marzano ◽  
Mariano Francesco Caratozzolo ◽  
Graziano Pesole ◽  
Elisabetta Sbisà ◽  
Apollonia Tullo
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
Therapeutic Target ◽  
Malignant Tumors ◽  
Premature Death ◽  
Chemotherapy Response ◽  
Protein Levels ◽  
Promising Therapeutic Target ◽  
Trim Proteins

Colorectal cancer (CRC) represents one of the most widespread forms of cancer in the population and, as all malignant tumors, often develops resistance to chemotherapies with consequent tumor growth and spreading leading to the patient’s premature death. For this reason, a great challenge is to identify new therapeutic targets, able to restore the drugs sensitivity of cancer cells. In this review, we discuss the role of TRIpartite Motifs (TRIM) proteins in cancers and in CRC chemoresistance, focusing on the tumor-suppressor role of TRIM8 protein in the reactivation of the CRC cells sensitivity to drugs currently used in the clinical practice. Since the restoration of TRIM8 protein levels in CRC cells recovers chemotherapy response, it may represent a new promising therapeutic target in the treatment of CRC.

scholarly journals A novel mitochondrial Kv1.3–caveolin axis controls cell survival and apoptosis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jesusa Capera ◽  
Mireia Pérez-Verdaguer ◽  
Roberta Peruzzo ◽  
María Navarro-Pérez ◽  
Juan Martínez-Pinna ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Survival ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Membrane Microdomains ◽  
Functional Link ◽  
Caveolin 1 ◽  
Molecular Determinants ◽  
Apoptotic Effects

The voltage-gated potassium channel Kv1.3 plays an apparent dual physiological role by participating in activation and proliferation of leukocytes as well as promoting apoptosis in several types of tumor cells. Therefore, Kv1.3 is considered a potential pharmacological target for immunodeficiency and cancer. Different cellular locations of Kv1.3, at the plasma membrane or the mitochondria, could be responsible for such duality. While plasma membrane Kv1.3 facilitates proliferation, the mitochondrial channel modulates apoptotic signaling. Several molecular determinants of Kv1.3 drive the channel to the cell surface, but no information is available about its mitochondrial targeting. Caveolins, which are able to modulate cell survival, participate in the plasma membrane targeting of Kv1.3. The channel, via a caveolin-binding domain (CDB), associates with caveolin 1 (Cav1), which localizes Kv1.3 to lipid raft membrane microdomains. The aim of our study was to understand the role of such interactions not only for channel targeting but also for cell survival in mammalian cells. By using a caveolin association-deficient channel (Kv1.3 CDBless), we demonstrate here that while the Kv1.3–Cav1 interaction is responsible for the channel localization in the plasma membrane, a lack of such interaction accumulates Kv1.3 in the mitochondria. Kv1.3 CDBless severely affects mitochondrial physiology and cell survival, indicating that a functional link of Kv1.3 with Cav1 within the mitochondria modulates the pro-apoptotic effects of the channel. Therefore, the balance exerted by these two complementary mechanisms fine-tune the physiological role of Kv1.3 during cell survival or apoptosis. Our data highlight an unexpected role for the mitochondrial caveolin–Kv1.3 axis during cell survival and apoptosis.

scholarly journals Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1558 ◽  
Author(s):  
Iman Abdelaziz Mohamed ◽  
Alain-Pierre Gadeau ◽  
Anwarul Hasan ◽  
Nabeel Abdulrahman ◽  
Fatima Mraiche
Keyword(s):  
Heart Failure ◽  
Tissue Regeneration ◽  
Cardiac Remodeling ◽  
Therapeutic Target ◽  
Cardiac Fibrosis ◽  
Matricellular Protein ◽  
Physiological Conditions ◽  
Intracellular Signals ◽  
Promising Therapeutic Target

Osteopontin (OPN) is recognized for its significant roles in both physiological and pathological processes. Initially, OPN was recognized as a cytokine with pro-inflammatory actions. More recently, OPN has emerged as a matricellular protein of the extracellular matrix (ECM). OPN is also known to be a substrate for proteolytic cleavage by several proteases that form an integral part of the ECM. In the adult heart under physiological conditions, basal levels of OPN are expressed. Increased expression of OPN has been correlated with the progression of cardiac remodeling and fibrosis to heart failure and the severity of the condition. The intricate process by which OPN mediates its effects include the coordination of intracellular signals necessary for the differentiation of fibroblasts into myofibroblasts, promoting angiogenesis, wound healing, and tissue regeneration. In this review, we discuss the role of OPN in contributing to the development of cardiac fibrosis and its suitability as a therapeutic target.

Role of the potassium channel KCa3.1 in diabetic nephropathy

2014 ◽  
Vol 127 (7) ◽  
pp. 423-433 ◽  
Author(s):  
Chunling Huang ◽  
Carol A. Pollock ◽  
Xin-Ming Chen
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Target ◽  
Functional Decline ◽  
Physiological Role ◽  
Inflammatory Cells ◽  
Tubulointerstitial Fibrosis ◽  
K Channel ◽  
Proximal Tubular ◽  
Progressive Renal Disease

There is an urgent need to identify novel interventions for mitigating the progression of diabetic nephropathy. Diabetic nephropathy is characterized by progressive renal fibrosis, in which tubulointerstitial fibrosis has been shown to be the final common pathway of all forms of chronic progressive renal disease, including diabetic nephropathy. Therefore targeting the possible mechanisms that drive this process may provide novel therapeutics which allow the prevention and potentially retardation of the functional decline in diabetic nephropathy. Recently, the Ca2+-activated K+ channel KCa3.1 (KCa3.1) has been suggested as a potential therapeutic target for nephropathy, based on its ability to regulate Ca2+ entry into cells and modulate Ca2+-signalling processes. In the present review, we focus on the physiological role of KCa3.1 in those cells involved in the tubulointerstitial fibrosis, including proximal tubular cells, fibroblasts, inflammatory cells (T-cells and macrophages) and endothelial cells. Collectively these studies support further investigation into KCa3.1 as a therapeutic target in diabetic nephropathy.

scholarly journals The Role of Autophagy Modulated by Exercise in Cancer Cachexia

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 781
Author(s):  
Julia Windi Gunadi ◽  
Ariyani Sudhamma Welliangan ◽  
Ray Sebastian Soetadji ◽  
Diana Krisanti Jasaputra ◽  
Ronny Lesmana
Keyword(s):  
Muscle Atrophy ◽  
Muscle Function ◽  
Cancer Cachexia ◽  
Physiological Role ◽  
Energy Utilization ◽  
Patients With Cancer ◽  
Different Types ◽  
Exercise Type ◽  
Type Of Exercise

Cancer cachexia is a syndrome experienced by many patients with cancer. Exercise can act as an autophagy modulator, and thus holds the potential to be used to treat cancer cachexia. Autophagy imbalance plays an important role in cancer cachexia, and is correlated to skeletal and cardiac muscle atrophy and energy-wasting in the liver. The molecular mechanism of autophagy modulation in different types of exercise has not yet been clearly defined. This review aims to elaborate on the role of exercise in modulating autophagy in cancer cachexia. We evaluated nine studies in the literature and found a potential correlation between the type of exercise and autophagy modulation. Combined exercise or aerobic exercise alone seems more beneficial than resistance exercise alone in cancer cachexia. Looking ahead, determining the physiological role of autophagy modulated by exercise will support the development of a new medical approach for treating cancer cachexia. In addition, the harmonization of the exercise type, intensity, and duration might play a key role in optimizing the autophagy levels to preserve muscle function and regulate energy utilization in the liver.

scholarly journals Promising therapeutic role of miR-27b in tumor

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769165 ◽  
Author(s):  
Li Ding ◽  
Jie Ni ◽  
Fan Yang ◽  
Lingli Huang ◽  
Heng Deng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Target ◽  
Biological Pathways ◽  
Molecular Targeting ◽  
Gene Clustering ◽  
Biological Processes ◽  
Targeting Therapy ◽  
Human Cancers ◽  
Promising Therapeutic Target

MicroRNAs are small nonprotein-encoding RNAs ranging from 18 to 25 nucleotides in size and regulate multiple biological pathways via directly targeting a variety of associated genes in cancers. MicroRNA-27b is a highly conserved MicroRNA throughout vertebrates and there are two homologs (hsa-miR-27a and hsa-miR-27b) in humans. MicroRNA-27b is an intragenic microRNA located on chromosome 9q22.1 within the C9orf3 gene, clustering with miR-23b and miR-24-1 in human. As a frequently dysregulated microRNA in human cancers, microRNA-27b could function as a tumor suppressor or an oncogenic microRNA. More and more studies indicate that microRNA-27b is involved in affecting various biological processes, such as angiogenesis, proliferation, metastasis, and drug resistance, and thus may act as a promising therapeutic target in human cancers. In this review, we discuss the role of microRNA-27b in detail and offer novel insights into molecular targeting therapy for cancers.

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