scholarly journals Toll-like Receptors Signaling Pathways as a Potential Therapeutic Target in Cardiovascular Disease

2018 ◽  
Vol 24 (17) ◽  
pp. 1887-1898 ◽  
Author(s):  
Seyed Mostafa Parizadeh ◽  
Maryam Ghandehari ◽  
Motahareh Heydari-majd ◽  
Sima Seifi ◽  
Ramin Mardani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Immune System ◽  
Signaling Pathways ◽  
Cardiac Remodeling ◽  
Therapeutic Target ◽  
Good Evidence ◽  
Toll Like Receptors ◽  
Potential Therapeutic Target

Cardiovascular Disease (CVD) is one of the most important causes of morbidity and mortality, and associated with an important economic burden globally. Over the last decade, the prevalence of CVD has been rising globally, and is now associated with millions of death annually in both developed and developing countries. There is good evidence that the immune system is involved in the pathophysiology of CVD. Toll-like receptors (TLRs) and their down-stream signaling pathways play an important role in the immune system. Recent studies have suggested that the TLRs are involved in atherogenesis, including stroke, myocardial infarction, ischemiareperfusion injury, cardiac remodeling and development of Heart Failure (HF). In this review we have summarized the recent studies investigating the role of TLRs in CVD and the potential for using TLRs signaling pathways as a therapeutic target in CVD.

scholarly journals Intracellular and Extracellular Roles of Granzyme K

2021 ◽  
Vol 12 ◽  
Author(s):  
Annemieke C. Bouwman ◽  
Kim R. van Daalen ◽  
Sandra Crnko ◽  
Toine ten Broeke ◽  
Niels Bovenschen
Keyword(s):  
Immune System ◽  
Therapeutic Target ◽  
Serine Proteases ◽  
Bacterial Infections ◽  
Thermal Injury ◽  
Current Knowledge ◽  
Endothelial Activation ◽  
Potential Therapeutic Target ◽  
Cytotoxic Cells

Granzymes are a family of serine proteases stored in granules inside cytotoxic cells of the immune system. Granzyme K (GrK) has been only limitedly characterized and knowledge on its molecular functions is emerging. Traditionally GrK is described as a granule-secreted, pro-apoptotic serine protease. However, accumulating evidence is redefining the functions of GrK by the discovery of novel intracellular (e.g. cytotoxicity, inhibition of viral replication) and extracellular roles (e.g. endothelial activation and modulation of a pro-inflammatory immune cytokine response). Moreover, elevated GrK levels are associated with disease, including viral and bacterial infections, airway inflammation and thermal injury. This review aims to summarize and discuss the current knowledge of i) intracellular and extracellular GrK activity, ii) cytotoxic and non-cytotoxic GrK functioning, iii) the role of GrK in disease, and iv) GrK as a potential therapeutic target.

scholarly journals The Role of Notch Signaling in Macrophages during Inflammation and Infection: Implication in Rheumatoid Arthritis?

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 111 ◽  
Author(s):  
Esra’a Keewan ◽  
Saleh A. Naser
Keyword(s):  
Rheumatoid Arthritis ◽  
Notch Signaling ◽  
Signaling Pathways ◽  
Therapeutic Target ◽  
Limited Data ◽  
Potential Therapeutic Target ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Infection And Inflammation

Notch signaling coordinates numerous cellular processes and has been implicated in many pathological conditions, including rheumatoid arthritis (RA). Although the role of Notch signaling in development, maturation, differentiation, and activation of lymphocytes has been comprehensively reported, less is known about its role in myeloid cells. Certainly, limited data are available about the role of Notch signaling in macrophages during inflammation and infection. In this review, we discuss the recent advances pertaining to the role of Notch signaling in differentiation, activation, and metabolism of macrophages during inflammation and infection. We also highlight the reciprocal interplay between Notch signaling and other signaling pathways in macrophages under different inflammatory and infectious conditions including pathogenesis of RA. Finally, we discuss approaches that could consider Notch signaling as a potential therapeutic target against infection- and inflammation-driven diseases.

Involvement of monocytes/macrophages as key factors in the development and progression of cardiovascular diseases

2014 ◽  
Vol 458 (2) ◽  
pp. 187-193 ◽  
Author(s):  
María Fernández-Velasco ◽  
Silvia González-Ramos ◽  
Lisardo Boscá
Keyword(s):  
Myocardial Infarction ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Initial Period ◽  
Cardiac Injury ◽  
Key Factors ◽  
Cardiac Damage ◽  
Inflammatory Profile

Emerging evidence points to the involvement of specialized cells of the immune system as key drivers in the pathophysiology of cardiovascular diseases. Monocytes are an essential cell component of the innate immune system that rapidly mobilize from the bone marrow to wounded tissues where they differentiate into macrophages or dendritic cells and trigger an immune response. In the healthy heart a limited, but near-constant, number of resident macrophages have been detected; however, this number significantly increases during cardiac damage. Shortly after initial cardiac injury, e.g. myocardial infarction, a large number of macrophages harbouring a pro-inflammatory profile (M1) are rapidly recruited to the cardiac tissue, where they contribute to cardiac remodelling. After this initial period, resolution takes place in the wound, and the infiltrated macrophages display a predominant deactivation/pro-resolution profile (M2), promoting cardiac repair by mediating pro-fibrotic responses. In the present review we focus on the role of the immune cells, particularly in the monocyte/macrophage population, in the progression of the major cardiac pathologies myocardial infarction and atherosclerosis.

scholarly journals The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Manqiu Ding ◽  
Yongqiang Chen ◽  
Yue Lang ◽  
Li Cui
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Cell Survival ◽  
Cancer Cells ◽  
Prion Protein ◽  
Therapeutic Target ◽  
Cancer Biology ◽  
Cellular Prion Protein ◽  
Potential Therapeutic Target

Prion protein has two isoforms including cellular prion protein (PrPC) and scrapie prion protein (PrPSc). PrPSc is the pathological aggregated form of prion protein and it plays an important role in neurodegenerative diseases. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein that can attach to a membrane. Its expression begins at embryogenesis and reaches the highest level in adulthood. PrPC is expressed in the neurons of the nervous system as well as other peripheral organs. Studies in recent years have disclosed the involvement of PrPC in various aspects of cancer biology. In this review, we provide an overview of the current understanding of the roles of PrPC in proliferation, cell survival, invasion/metastasis, and stem cells of cancer cells, as well as its role as a potential therapeutic target.

scholarly journals SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis

2021 ◽  
Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Experimental Verification ◽  
Inflammatory Disease ◽  
Therapeutic Target ◽  
Tyrosine Phosphatase ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Potential Therapeutic Target ◽  
Single Cell Rna Sequencing

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.

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