Targeting the Sphingolipid System as a Therapeutic Direction for Glioblastoma

Glioblastoma (GBM) is the most commonly diagnosed malignant brain tumor in adults. The prognosis for patients with GBM remains poor and largely unchanged over the last 30 years, due to the limitations of existing therapies. Thus, new therapeutic approaches are desperately required. Sphingolipids are highly enriched in the brain, forming the structural components of cell membranes, and are major lipid constituents of the myelin sheaths of nerve axons, as well as playing critical roles in cell signaling. Indeed, a number of sphingolipids elicit a variety of cellular responses involved in the development and progression of GBM. Here, we discuss the role of sphingolipids in the pathobiology of GBM, and how targeting sphingolipid metabolism has emerged as a promising approach for the treatment of GBM.

Download Full-text

Kisspeptins in physiology and pathology of sex development - new diagnostic and therapeutic approaches

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf1243-12 ◽

2014 ◽

Vol 12 (4) ◽

pp. 3-12

Author(s):

Irina Leorovna Nikitina ◽

Alekber Azizovich Bayramov ◽

Yuliya Nikolaevna Khoduleva ◽

Petr Dmitriyevich Shabanov

Keyword(s):

Reproductive System ◽

Sexual Differentiation ◽

System Development ◽

Therapeutic Approaches ◽

New Therapeutic Approaches ◽

Sex Development ◽

Human Reproductive ◽

Modern Knowledge ◽

The Brain

The article is dedicated to mechanisms of the human reproductive system development mechanisms. The evolution of the opinions on that processes was analysed. The review of modern knowledge of molecular and genetic causes of sex development, new mechanisms of gonadal axis regulation and role of kisspeptins in pubertat start and sexual differentiation of the brain are presented. The new actual directions of scientific research as well as the applications of kisspeptin drugs for new therapeutic approaches, treatment of hormone-dependent diseases and abnormalities of sex developmentare are observed.

Download Full-text

Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon

Cells ◽

10.3390/cells9020350 ◽

2020 ◽

Vol 9 (2) ◽

pp. 350 ◽

Cited By ~ 2

Author(s):

Alessandro Zambusi ◽

Özge Pelin Burhan ◽

Rossella Di Giaimo ◽

Bettina Schmid ◽

Jovica Ninkovic

Keyword(s):

Premature Aging ◽

Therapeutic Approaches ◽

Human Microglia ◽

Transcriptional Signature ◽

New Therapeutic Approaches ◽

Inflammatory Phenotype ◽

Transcriptional Changes ◽

Aging Kinetics ◽

The Brain

Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.

Download Full-text

The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: dark and light sides of the force

Pharmacological Reports ◽

10.1007/s43440-021-00315-2 ◽

2021 ◽

Author(s):

Natalia Bryniarska-Kubiak ◽

Andrzej Kubiak ◽

Małgorzata Lekka ◽

Agnieszka Basta-Kaim

Keyword(s):

Nervous System ◽

Physical Factors ◽

Nervous System Diseases ◽

Therapeutic Approaches ◽

System Disease ◽

New Therapeutic Approaches ◽

The Subject ◽

Topographical Factors ◽

New Treatment

AbstractNervous system diseases are the subject of intensive research due to their association with high mortality rates and their potential to cause irreversible disability. Most studies focus on targeting the biological factors related to disease pathogenesis, e.g. use of recombinant activator of plasminogen in the treatment of stroke. Nevertheless, multiple diseases such as Parkinson’s disease and Alzheimer’s disease still lack successful treatment. Recently, evidence has indicated that physical factors such as the mechanical properties of cells and tissue and topography play a crucial role in homeostasis as well as disease progression. This review aims to depict these factors’ roles in the progression of nervous system diseases and consequently discusses the possibility of new therapeutic approaches. The literature is reviewed to provide a deeper understanding of the roles played by physical factors in nervous system disease development to aid in the design of promising new treatment approaches. Graphic abstract

Download Full-text

Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

Experimental Cell Research ◽

10.1016/j.yexcr.2013.12.029 ◽

2014 ◽

Vol 325 (2) ◽

pp. 58-64 ◽

Cited By ~ 29

Author(s):

Tuula Salo ◽

Marilena Vered ◽

Ibrahim O. Bello ◽

Pia Nyberg ◽

Carolina Cavalcante Bitu ◽

...

Keyword(s):

Tumor Microenvironment ◽

Oral Carcinoma ◽

Therapeutic Approaches ◽

New Therapeutic Approaches

Download Full-text

The human brain: Chairman’s introduction

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1981.0023 ◽

1981 ◽

Vol 292 (1057) ◽

pp. 151-153

Keyword(s):

Human Brain ◽

Cultural Evolution ◽

Positive Feedback ◽

Time Scale ◽

Biological Evolution ◽

Internal Models ◽

Adaptive Behaviour ◽

Myelin Sheaths ◽

The Brain

Much has been said at the symposium about the pre-eminent role of the brain in the continuing emergence of man. Tobias has spoken of its explosive enlargement during the last 1 Ma, and how much of its enlargement in individual ontogeny is postnatal. We are born before our brains are fully grown and ‘wired up ’. During our long adolescence we build up internal models of the outside world and of the relations of parts of our bodies to it and to one another. Neurons that are present at birth spread their dendrites and project axons which acquire their myelin sheaths, and establish innumerable contacts with other neurons, over the years. New connections are formed; genetically endowed ones are stamped in or blanked off. People born without arms may grow up to use their toes in skills that are normally manual. Tobias, Darlington and others have stressed the enormous survival value of adaptive behaviour and the ‘positive feedback’ relation between biological and cultural evolution. The latter, the unique product of the unprecedentedly rapid biological evolution of big brains, advances on a time scale unknown to biological evolution.

Download Full-text

P50. Role of glioma produced CM1 in the brain tumor tropism of human neural stem cells

Differentiation ◽

10.1016/j.diff.2010.09.056 ◽

2010 ◽

Vol 80 ◽

pp. S33-S34

Author(s):

J. Jeon ◽

S. Cho ◽

K. Cho ◽

Y. Lee ◽

M. Lee

Keyword(s):

Stem Cells ◽

Brain Tumor ◽

Neural Stem Cells ◽

Human Neural Stem Cells ◽

Tumor Tropism ◽

The Brain

Download Full-text

Non-Cell Autonomous and Epigenetic Mechanisms of Huntington’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms222212499 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12499

Author(s):

Chaebin Kim ◽

Ali Yousefian-Jazi ◽

Seung-Hye Choi ◽

Inyoung Chang ◽

Junghee Lee ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Trinucleotide Repeat ◽

Neurodegenerative Disorder ◽

Involuntary Movement ◽

Therapeutic Approaches ◽

Exon 1 ◽

Human Chromosome 4 ◽

The Brain

Huntington’s disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of Huntingtin (HTT) gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this review, we address the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs). We also discuss how mHTT modulates epigenetic modifications and transcriptional pathways in MSNs. In addition, we define how non-cell autonomous pathways lead to damage and death of MSNs under HD pathological conditions. Lastly, we overview therapeutic approaches for HD. Together, understanding of precise neuropathological mechanisms of HD may improve therapeutic approaches to treat the onset and progression of HD.

Download Full-text

Neuroinflammation in Huntington’s disease: A starring role for astrocyte and microglia

Current Neuropharmacology ◽

10.2174/1570159x19666211201094608 ◽

2021 ◽

Vol 19 ◽

Author(s):

Julieta Saba ◽

Federico López Couselo ◽

Julieta Bruno ◽

Lila Carniglia ◽

Daniela Durand ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Genetic Disorder ◽

Cag Repeat ◽

Inflammatory Factors ◽

Therapeutic Approaches ◽

Reactive Microglia ◽

New Treatments ◽

The Brain

: Huntington’s disease (HD) is a neurodegenerative genetic disorder caused by a CAG repeat expansion in the huntingtin gene. HD causes motor, cognitive, and behavioral dysfunction. Since no existing treatment affects the course of this disease, new treatments are needed. Inflammation is frequently observed in HD patients before symptom onset. Neuroinflammation, characterized by the presence of reactive microglia and astrocytes and inflammatory factors within the brain, is also detected early. However, in comparison with other neurodegenerative diseases, the role of neuroinflammation in HD is much less known. Work has been dedicated to altered microglial and astrocytic functions in the context of HD, but less attention has been given to glial participation in neuroinflammation. This review describes evidence of inflammation in HD patients and animal models. It also discusses recent knowledge on neuroinflammation in HD, highlighting astrocyte and microglia involvement in the disease and considering anti-inflammatory therapeutic approaches.

Download Full-text

The Gut Ecosystem: A Critical Player in Stroke

NeuroMolecular Medicine ◽

10.1007/s12017-020-08633-z ◽

2020 ◽

Author(s):

Rosa Delgado Jiménez ◽

Corinne Benakis

Keyword(s):

Current Knowledge ◽

Critical Factor ◽

Intestinal Microbiome ◽

Brain Disorders ◽

Therapeutic Approaches ◽

Health And Disease ◽

Brain Stroke ◽

The Brain ◽

Improve Patient

AbstractThe intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

Download Full-text

Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

Diagnostics ◽

10.3390/diagnostics10040192 ◽

2020 ◽

Vol 10 (4) ◽

pp. 192

Author(s):

Leonie Konczalla ◽

Anna Wöstemeier ◽

Marius Kemper ◽

Karl-Frederik Karstens ◽

Jakob Izbicki ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Clinical Application ◽

Liquid Biopsy ◽

Cancer Diagnostics ◽

Therapeutic Approaches ◽

Primary Tumors ◽

New Therapeutic Approaches ◽

Tumor Dissemination

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

Download Full-text