scholarly journals Targeting the Ghrelin Receptor as a Novel Therapeutic Option for Epilepsy

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 53
Author(s):  
An Buckinx ◽  
Dimitri De Bundel ◽  
Ron Kooijman ◽  
Ilse Smolders
Keyword(s):  
Current Knowledge ◽  
Therapeutic Option ◽  
Endogenous Ligand ◽  
Pharmacoresistant Epilepsy ◽  
Ghrelin Receptor ◽  
Downstream Signaling ◽  
Broad Array ◽  
Epilepsy Models ◽  
Anticonvulsant Effects ◽  
Novel Therapeutic

Epilepsy is a neurological disease affecting more than 50 million individuals worldwide. Notwithstanding the availability of a broad array of antiseizure drugs (ASDs), 30% of patients suffer from pharmacoresistant epilepsy. This highlights the urgent need for novel therapeutic options, preferably with an emphasis on new targets, since “me too” drugs have been shown to be of no avail. One of the appealing novel targets for ASDs is the ghrelin receptor (ghrelin-R). In epilepsy patients, alterations in the plasma levels of its endogenous ligand, ghrelin, have been described, and various ghrelin-R ligands are anticonvulsant in preclinical seizure and epilepsy models. Up until now, the exact mechanism-of-action of ghrelin-R-mediated anticonvulsant effects has remained poorly understood and is further complicated by multiple downstream signaling pathways and the heteromerization properties of the receptor. This review compiles current knowledge, and discusses the potential mechanisms-of-action of the anticonvulsant effects mediated by the ghrelin-R.

scholarly journals Tissue Factor: A Conventional or Alternative Target in Cancer Therapy

2016 ◽  
Vol 62 (4) ◽  
pp. 563-570 ◽  
Author(s):  
Andreas Eisenreich ◽  
Juliane Bolbrinker ◽  
Ulrike Leppert
Keyword(s):  
Tissue Factor ◽  
Cancer Biology ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Protein Isoforms ◽  
Downstream Signaling ◽  
Alternatively Spliced ◽  
Membrane Bound ◽  
Tumor Growth And Metastasis ◽  
Novel Therapeutic

Abstract BACKGROUND Tissue factor (TF) is an evolutionary conserved glycoprotein that plays an important role in the pathogenesis of cancer. TF is expressed in 2 naturally occurring protein isoforms, membrane-bound full-length (fl)TF and soluble alternatively spliced (as)TF. Both isoforms have been shown to affect a variety of pathophysiologically relevant functions, such as tumor-associated angiogenesis, thrombogenicity, tumor growth, and metastasis. Therefore, targeting TF either by direct inhibition or indirectly, i.e., on a posttranscriptional level, offers a novel therapeutic option for cancer treatment. CONTENT In this review we summarize the latest findings regarding the role of TF and its isoforms in cancer biology. Moreover, we briefly depict and discuss the therapeutic potential of direct and/or indirect inhibition of TF activity and expression for the treatment of cancer. SUMMARY asTF and flTF play important and often distinct roles in cancer biology, i.e., in thrombogenicity and angiogenesis, which is mediated by isoform-specific signal transduction pathways. Therefore, both TF isoforms and downstream signaling are promising novel therapeutic targets in malignant diseases.

Copper-impregnated socks: A novel therapeutic option for combating occupational dermatophytosis

2021 ◽  
Author(s):  
Sukriti Baveja ◽  
Chetan C. Patil ◽  
Surbhi Vashisht ◽  
Deepak Vashisht ◽  
Vikas Pathania ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Novel Therapeutic

Postischemic Revascularization: From Cellular and Molecular Mechanisms to Clinical Applications

2013 ◽  
Vol 93 (4) ◽  
pp. 1743-1802 ◽  
Author(s):  
Jean-Sébastien Silvestre ◽  
David M. Smadja ◽  
Bernard I. Lévy
Keyword(s):  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Vascular Wall ◽  
Arterial Disease ◽  
Cellular Mechanisms ◽  
Collateral Growth ◽  
Vessel Growth ◽  
Ischemic Diseases

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

Erythropoietin — A Novel Therapeutic Option for Cachectic Patients

2005 ◽  
pp. 407-424
Author(s):  
Ewa Jankowska ◽  
Piotr Ponikowski ◽  
Waldemar Banasiak
Keyword(s):  
Therapeutic Option ◽  
Novel Therapeutic

scholarly journals Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1942
Author(s):  
Stefania Pizzimenti ◽  
Simone Ribero ◽  
Marie Angele Cucci ◽  
Margherita Grattarola ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Targeted Therapies ◽  
Current Knowledge ◽  
Mapk Pathway ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Advanced Melanoma ◽  
Braf Mutations ◽  
Downstream Signaling ◽  
Activating Mutations

Melanoma is a highly aggressive cancer with the poorest prognosis, representing the deadliest form of skin cancer. Activating mutations in BRAF are the most frequent genetic alterations, present in approximately 50% of all melanoma cases. The use of specific inhibitors towards mutant BRAF variants and MEK, a downstream signaling target of BRAF in the MAPK pathway, has significantly improved progression-free and overall survival in advanced melanoma patients carrying BRAF mutations. Nevertheless, despite these improvements, resistance still develops within the first year of therapy in around 50% of patients, which is a significant problem in managing BRAF-mutated advanced melanoma. Understanding these mechanisms is one of the mainstreams of the research on BRAFi/MEKi acquired resistance. Both genetic and epigenetic mechanisms have been described. Moreover, in recent years, oxidative stress has emerged as another major force involved in all the phases of melanoma development, from initiation to progression until the onsets of the metastatic phenotype and chemoresistance, and has thus become a target for therapy. In the present review, we discuss the current knowledge on oxidative stress and its signaling in melanoma, as well as the oxidative stress-related mechanisms in the acquired resistance to targeted therapies.

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