scholarly journals O-acetylated Gangliosides as Targets for Cancer Immunotherapy

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 741 ◽  
Author(s):  
Sumeyye Cavdarli ◽  
Philippe Delannoy ◽  
Sophie Groux-Degroote

O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions. O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl-O-acetyltransferases (SOAT) described until now. O-acetylated ganglioside species are mainly expressed during embryonic development and in the central nervous system in healthy adults, but are re-expressed during cancer development and are considered as markers of cancers of neuroectodermal origin. However, the specific biological roles of O-acetylated gangliosides in developing and malignant tissues have not been extensively studied, mostly because of the requirement of specific approaches and tools for sample preparation and analysis. In this review, we summarize our current knowledge of ganglioside biosynthesis and expression in normal and pathological conditions, of ganglioside O-acetylation analysis and expression in cancers, and of the possible use of O-acetylated gangliosides as targets for cancer immunotherapy.

Author(s):  
Cristiana Pistono ◽  
Nea Bister ◽  
Iveta Stanová ◽  
Tarja Malm

Glial cells are crucial for the maintenance of correct neuronal functionality in a physiological state and intervene to restore the equilibrium when environmental or pathological conditions challenge central nervous system homeostasis. The communication between glial cells and neurons is essential and extracellular vesicles (EVs) take part in this function by transporting a plethora of molecules with the capacity to influence the function of the recipient cells. EVs, including exosomes and microvesicles, are a heterogeneous group of biogenetically distinct double membrane-enclosed vesicles. Once released from the cell, these two types of vesicles are difficult to discern, thus we will call them with the general term of EVs. This review is focused on the EVs secreted by astrocytes, oligodendrocytes and microglia, aiming to shed light on their influence on neurons and on the overall homeostasis of the central nervous system functions. We collect evidence on neuroprotective and homeostatic effects of glial EVs, including neuronal plasticity. On the other hand, current knowledge of the detrimental effects of the EVs in pathological conditions is addressed. Finally, we propose directions for future studies and we evaluate the potential of EVs as a therapeutic treatment for neurological disorders.


2021 ◽  
Vol 12 ◽  
Author(s):  
Min-Hyun Kim ◽  
Hyeyoung Kim

Leptin is a pluripotent peptide hormone produced mainly by adipocytes, as well as by other tissues such as the stomach. Leptin primarily acts on the central nervous system, particularly the hypothalamus, where this hormone regulates energy homeostasis and neuroendocrine function. Owing to this, disruption of leptin signaling has been linked with numerous pathological conditions. Recent studies have also highlighted the diverse roles of leptin in the digestive system including immune regulation, cell proliferation, tissue healing, and glucose metabolism. Of note, leptin acts differently under physiological and pathological conditions. Here, we review the current knowledge on the functions of leptin and its downstream signaling in the gastrointestinal tract and accessory digestive organs, with an emphasis on its physiological and pathological implications. We also discuss the current therapeutic uses of recombinant leptin, as well as its limitations.


2008 ◽  
Vol 364 (1515) ◽  
pp. 341-355 ◽  
Author(s):  
Daniela Tropea ◽  
Audra Van Wart ◽  
Mriganka Sur

A remarkable amount of our current knowledge of mechanisms underlying experience-dependent plasticity during cortical development comes from study of the mammalian visual cortex. Recent advances in high-resolution cellular imaging, combined with genetic manipulations in mice, novel fluorescent recombinant probes, and large-scale screens of gene expression, have revealed multiple molecular mechanisms that underlie structural and functional plasticity in visual cortex. We situate these mechanisms in the context of a new conceptual framework of feed-forward and feedback regulation for understanding how neurons of the visual cortex reorganize their connections in response to changes in sensory inputs. Such conceptual advances have important implications for understanding not only normal development but also pathological conditions that afflict the central nervous system.


2020 ◽  
Vol 20 (13) ◽  
pp. 1142-1153 ◽  
Author(s):  
Sreyashi Chandra ◽  
Md. Tanjim Alam ◽  
Jhilik Dey ◽  
Baby C. Pulikkaparambil Sasidharan ◽  
Upasana Ray ◽  
...  

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington’s disease (HD). Objective: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. Methods: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. Results: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. Conclusion: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.


2017 ◽  
Vol 9 (12) ◽  
pp. 797-816 ◽  
Author(s):  
Zhi Yang ◽  
Shuai Jiang ◽  
Yicheng Cheng ◽  
Tian Li ◽  
Wei Hu ◽  
...  

Forkhead box C1 (FOXC1) is an essential member of the forkhead box transcription factors and has been highlighted as an important transcriptional regulator of crucial proteins associated with a wide variety of carcinomas. FOXC1 regulates tumor-associated genes and is regulated by multiple pathways that control its mRNA expression and protein activity. Aberrant FOXC1 expression is involved in diverse tumorigenic processes, such as abnormal cell proliferation, cancer stem cell maintenance, cancer migration, and angiogenesis. Herein, we review the correlation between the expression of FOXC1 and tumor behaviors. We also summarize the mechanisms of the regulation of FOXC1 expression and activity in physiological and pathological conditions. In particular, we focus on the pathological processes of cancer targeted by FOXC1 and discuss whether FOXC1 is good or detrimental during tumor progression. Moreover, FOXC1 is highlighted as a clinical biomarker for diagnosis or prognosis in various human cancers. The information reviewed here should assist in experimental designs and emphasize the potential of FOXC1 as a therapeutic target for cancer.


Author(s):  
Katarzyna Curzytek ◽  
Monika Leśkiewicz

AbstractSince affective disorders are considered to be underlain by the immune system malfunction, an important role in their pathophysiology is assigned to the proinflammatory mediators. Recently, chemokines, the group of chemotactic cytokines, have become a focus for basic and clinical scientists in the context of the development and treatment of brain diseases. Among them, chemokine CCL2 and its main receptor CCR2 have become candidate mediators of abnormal brain-immune system dialogue in depression. Besides the chemotactic activity, the CCL2-CCR2 axis is involved in various neurobiological processes, neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, as well as neuroregeneration. Given the range of immunomodulatory possibilities that the CCL2-CCR2 pair can exert on the nervous system, its proinflammatory properties were initially thought to be a major contributor to the development of depressive disorders. However, further research suggests that the malfunctions of the nervous system are rather associated with impaired homeostatic properties manifested by the CCL2-CCR2 dyad dysfunctions. This review aims to present literature data on the action of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions, as well as the contribution of this ligand-receptor system to the processes underlying affective disorders. Additionally, this article draws attention to the importance of the CCL2-CRR2 pathway as a potential pharmacological target with antidepressant potential.


Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 846
Author(s):  
Gitishree Das ◽  
Han-Seung Shin ◽  
Rosa Tundis ◽  
Sandra Gonçalves ◽  
Ourlad Alzeus G. Tantengco ◽  
...  

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.


2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fabien Pifferi ◽  
Benoit Laurent ◽  
Mélanie Plourde

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.


2014 ◽  
Vol 3 (1) ◽  
Author(s):  
Claudia Campanella ◽  
Celeste Caruso Bavisotto ◽  
Antonella Marino Gammazza ◽  
Dragana Nikolic ◽  
Francesca Rappa ◽  
...  

Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.


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