scholarly journals Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

2021 ◽  
Author(s):  
Joanna Ewa Sowa ◽  
Krzysztof Tokarski
Keyword(s):  
Glial Cells ◽  
Network Effects ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Neurological Impairment ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Biased Signaling ◽  
New Treatment

AbstractAccumulating evidence highlights chemokines as key mediators of the bidirectional crosstalk between neurons and glial cells aimed at preserving brain functioning. The multifaceted role of these immune proteins in the CNS is mirrored by the complexity of the mechanisms underlying its biological function, including biased signaling. Neurons, only in concert with glial cells, are essential players in the modulation of brain homeostatic functions. Yet, attempts to dissect these complex multilevel mechanisms underlying coordination are still lacking. Therefore, the purpose of this review is to summarize the current knowledge about mechanisms underlying chemokine regulation of neuron–glia crosstalk linking molecular, cellular, network, and behavioral levels. Following a brief description of molecular mechanisms by which chemokines interact with their receptors and then summarizing cellular patterns of chemokine expression in the CNS, we next delve into the sequence and mechanisms of chemokine-regulated neuron–glia communication in the context of neuroprotection. We then define the interactions with other neurotransmitters, neuromodulators, and gliotransmitters. Finally, we describe their fine-tuning on the network level and the behavioral relevance of their modulation. We believe that a better understanding of the sequence and nature of events that drive neuro-glial communication holds promise for the development of new treatment strategies that could, in a context- and time-dependent manner, modulate the action of specific chemokines to promote brain repair and reduce the neurological impairment.

scholarly journals Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior

2021 ◽  
Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Middle Phase ◽  
Temporal Shift

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.

scholarly journals MODERN TRENDS OF BASIC RESEARCH IN PATHOGENESIS OF PROGRESSIVE MYOPIA

2015 ◽  
Vol 69 (3-4) ◽  
pp. 44-49
Author(s):  
E. N. Iomdina ◽  
E. P. Tarutta
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Basic Research ◽  
Individual Treatment ◽  
Myopia Progression ◽  
Neural Processes ◽  
Treatment Plans ◽  
Progressive Myopia ◽  
New Treatment ◽  
And Control

The growing prevalence of progressive myopia and its disabling consequences explains the elaboration of reliable diagnostic markers and new treatment strategies based on the research results of molecular mechanisms underlying the development of the condition. The paper reviews recent basic pathogenetic research studies which have greatly broadened the awareness of the deep causes of progressive myopia associated with the activity of certain growth factors, local and systemic protein metabolism, and regulation of hormonal and neural processes. Practical clinical guidelines for new criteria of diagnosis and control of myopia are published as they could be useful while selecting individual treatment plans including indications to sclera-strengthening therapy and its evaluation. The results may be promising in the elaboration of systemic and local medications for the prevention of myopia progression, which should address the regulation of connective tissue disorders, hormonal shifts, and imbalanced autonomic nervous system. 

Recent advances in network medicine: From disease mechanisms to new treatment strategies

2020 ◽  
Vol 26 (5) ◽  
pp. 609-615
Author(s):  
Ítalo Faria do Valle
Keyword(s):  
Molecular Mechanisms ◽  
Biological Significance ◽  
Treatment Strategies ◽  
Molecular Networks ◽  
Network Medicine ◽  
Disease Mechanisms ◽  
Protein Interactome ◽  
Cellular Context ◽  
Human Proteins ◽  
New Treatment

Conventional reductionist approaches have guided most of our understanding in disease diagnostic and treatment. However, most diseases are not consequence of perturbations in a single protein or metabolite, but rather of the effect that these perturbations have in their cellular context. The emerging field of network medicine offers a set of tools to explore molecular networks and to retrieve insights about mechanisms of different diseases. The study of the protein interactome, the map of physical interactions among human proteins, revealed that disease proteins tend to interact with each other, linking diseases to well-defined interactome neighborhoods. These disease-associated neighborhoods have been defined as disease modules, and they can uncover the biological significance of genes identified by genetic studies, reveal molecular mechanisms that connect different phenotypes, and help identify new pharmacological strategies for disease treatment. Therefore, network medicine offers a framework in which the complexity of different aspects of multiple sclerosis can be explored in an integrative fashion, which can ultimately provide insights about disease mechanisms and treatment.

scholarly journals The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

2020 ◽  
Vol 21 (6) ◽  
pp. 2108 ◽  
Author(s):  
Wioletta Rozpędek-Kamińska ◽  
Natalia Siwecka ◽  
Adam Wawrzynkiewicz ◽  
Radosław Wojtczak ◽  
Dariusz Pytel ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Stress Conditions ◽  
World Population ◽  
Dependent Manner ◽  
Age Related ◽  
The Unfolded Protein Response

Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.

The intrinsic axon regenerative properties of mature neurons after injury

2020 ◽  
Author(s):  
Chunfeng Liu ◽  
Jinlian Liu ◽  
Chaoqun Liu ◽  
Qing Zhou ◽  
Yaodong Zhou ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Axon Regeneration ◽  
Treatment Strategies ◽  
Treatment Method ◽  
Signaling Cascades ◽  
Regulate Gene Expression ◽  
Mature Neurons ◽  
New Treatment ◽  
Multiple Signaling ◽  
Critical Process

Abstract Thousands of nerve injuries occur in the world each year. Axon regeneration is a very critical process for the restoration of the injured nervous system’s function. However, the precise molecular mechanism or signaling cascades that control axon regeneration are not clearly understood, especially in mammals. Therefore, there is almost no ideal treatment method to repair the nervous system’s injury until now. Mammalian axonal regeneration requires multiple signaling pathways to coordinately regulate gene expression in soma and assembly of the cytoskeleton protein in the growth cone. A better understanding of their molecular mechanisms, such as axon regeneration regulatory signaling cascades, will be helpful in developing new treatment strategies for promoting axon regeneration. In this review, we mainly focus on describing these regeneration-associated signaling cascades, which regulate axon regeneration.

Endometrial Cancer State of the Science Meeting

2009 ◽  
Vol 19 (1) ◽  
pp. 134-140 ◽  
Author(s):  
Henry C. Kitchener ◽  
Edward L. Trimble
Keyword(s):  
Endometrial Cancer ◽  
Current Knowledge ◽  
Gynecological Cancer ◽  
Treatment Strategies ◽  
List Type ◽  
Uterine Carcinosarcoma ◽  
National Cancer Research Institute ◽  
Key Issues ◽  
New Treatment ◽  
State Of The Science

There is a pressing need to improve our understanding of endometrial cancer (EC) and uterine carcinosarcoma and to develop new treatment strategies to improve outcomes. In recognition of this, a State of the Science meeting on EC was held last November 28 and 29, 2006, in Manchester, United Kingdom. The meeting was cosponsored by the National Cancer Research Institute (UK), the National Cancer Institute (US), and the Gynecological Cancer Intergroup.The objectives of the meeting were as follows: To review current knowledge and understanding of EC and its treatments.To identify key issues for translational research and clinical trials.To identify the most important trials for women with endometrial carcinoma and uterine carcinosarcoma, both those already underway or to be done, for which the Gynecological Cancer Intergroup might facilitate international cooperation.

Exosomal microRNAs in cancer-related sarcopenia: Tumor-derived exosomal microRNAs in muscle atrophy

2021 ◽  
pp. 153537022199032
Author(s):  
Chenyuan Li ◽  
Qi Wu ◽  
Zhiyu Li ◽  
Zhong Wang ◽  
Yi Tu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Degradation Pathways ◽  
Potential Treatment ◽  
Mass Wasting ◽  
Exosomal Mirnas ◽  
Cellular Components ◽  
Related Mortality

Cancer-associated sarcopenia is a complex metabolic syndrome marked by muscle mass wasting. Muscle wasting is a serious complication that is a primary contributor to cancer-related mortality. The underlying molecular mechanisms of cancer-associated sarcopenia have not been completely described to date. In general, evidence shows that the main pathophysiological alterations in sarcopenia are associated with the degradation of cellular components, an exceptional inflammatory secretome and mitochondrial dysfunction. Importantly, we highlight the prospect that several miRNAs carried by tumor-derived exosomes that have shown the ability to promote inflammatory secretion, activate catabolism, and even participate in the regulation of cellular degradation pathways can be delivered to and exert effects on muscle cells. In this review, we aim to describe the current knowledge about the functions of exosomal miRNAs in the induction of cancer-associated muscle wasting and propose potential treatment strategies.

scholarly journals The microenvironment in mature B-cell malignancies: a target for new treatment strategies

Blood ◽  
2009 ◽  
Vol 114 (16) ◽  
pp. 3367-3375 ◽  
Author(s):  
Jan A. Burger ◽  
Paolo Ghia ◽  
Andreas Rosenwald ◽  
Federico Caligaris-Cappio
Keyword(s):  
B Cell ◽  
Residual Disease ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
B Cell Malignancies ◽  
Accessory Cells ◽  
Specialized Tissue ◽  
New Treatment ◽  
Novel Strategy ◽  
Secondary Lymphoid Organs

AbstractDespite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts.

scholarly journals Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1496 ◽  
Author(s):  
Florian J. Raabe ◽  
Lenka Slapakova ◽  
Moritz J. Rossner ◽  
Ludovico Cantuti-Castelvetri ◽  
Mikael Simons ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Postmortem Brain ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Peripheral Tissues ◽  
Correlative Imaging ◽  
Postmortem Studies ◽  
New Treatment ◽  
Induced Pluripotent

Imaging and postmortem studies have revealed disturbed oligodendroglia-related processes in patients with schizophrenia and provided much evidence for disturbed myelination, irregular gene expression, and altered numbers of oligodendrocytes in the brains of schizophrenia patients. Oligodendrocyte deficits in schizophrenia might be a result of failed maturation and disturbed regeneration and may underlie the cognitive deficits of the disease, which are strongly associated with impaired long-term outcome. Cognition depends on the coordinated activity of neurons and interneurons and intact connectivity. Oligodendrocyte precursors form a synaptic network with parvalbuminergic interneurons, and disturbed crosstalk between these cells may be a cellular basis of pathology in schizophrenia. However, very little is known about the exact axon-glial cellular and molecular processes that may be disturbed in schizophrenia. Until now, investigations were restricted to peripheral tissues, such as blood, correlative imaging studies, genetics, and molecular and histological analyses of postmortem brain samples. The advent of human-induced pluripotent stem cells (hiPSCs) will enable functional analysis in patient-derived living cells and holds great potential for understanding the molecular mechanisms of disturbed oligodendroglial function in schizophrenia. Targeting such mechanisms may contribute to new treatment strategies for previously treatment-resistant cognitive symptoms.

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