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.

scholarly journals Applications of CRISPR/Cas9 in the research of malignant musculoskeletal tumors

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wei Liu ◽  
Shubin Wang ◽  
Binhui Lin ◽  
Wei Zhang ◽  
Guangrong Ji
Keyword(s):  
Malignant Tumors ◽  
Rapid Development ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Basic Research ◽  
Future Application ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Musculoskeletal Tumors ◽  
New Treatment

Abstract Background Malignant tumors of the musculoskeletal system, especially osteosarcoma, Ewing sarcoma and rhabdomyosarcoma, pose a major threat to the lives and health of adolescents and children. Current treatments for musculoskeletal tumors mainly include surgery, chemotherapy, and radiotherapy. The problems of chemotherapy resistance, poor long-term outcome of radiotherapy, and the inherent toxicity and side effects of chemical drugs make it extremely urgent to seek new treatment strategies. Main text As a potent gene editing tool, the rapid development of CRISPR/Cas9 technology in recent years has prompted scientists to apply it to the study of musculoskeletal tumors. This review summarizes the application of CRISPR/Cas9 technology for the treatment of malignant musculoskeletal tumors, focusing on its essential role in the field of basic research. Conclusion CRISPR, has demonstrated strong efficacy in targeting tumor-related genes, and its future application in the clinical treatment of musculoskeletal tumors is promising.

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.

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.

Molecular targets of lithium action

2003 ◽  
Vol 15 (6) ◽  
pp. 316-340 ◽  
Author(s):  
B Corbella ◽  
E Vieta
Keyword(s):  
Bipolar Disorder ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Mood Stabilizers ◽  
Lithium Cation ◽  
Therapeutic Effects ◽  
Term Outcome ◽  
Long Term Outcome ◽  
The Brain

Lithium is an effective drug for both the treatment and prophylaxis of bipolar disorder. However, the precise mechanism of lithium action is not yet well understood. Extensive research aiming to elucidate the molecular mechanisms underlying the therapeutic effects of lithium has revealed several possible targets. The behavioral and physiological manifestations of the illness are complex and are mediated by a network of interconnected neurotransmitter pathways. Thus, lithium's ability to modulate the release of serotonin at presynaptic sites and modulate receptor-mediated supersensitivity in the brain remains a relevant line of investigation. However, it is at the molecular level that some of the most exciting advances in the understanding of the long-term therapeutic action of lithium will continue in the coming years. The lithium cation possesses the selective ability, at clinically relevant concentrations, to alter the PI second-messenger system, potentially altering the activity and dynamic regulation of receptors that are coupled to this intracellular response. Subtypes of muscarinic receptors in the limbic system may represent particularly sensitive targets in this regard. Likewise, preclinical data have shown that lithium regulates arachidonic acid and the protein kinase C signaling cascades. It also indirectly regulates a number of factors involved in cell survival pathways, including cAMP response element binding protein, brain-derived neurotrophic factor, bcl-2 and mitogen-activated protein kinases, and may thus bring about delayed long-term beneficial effects via under-appreciated neurotrophic effects. Identification of the molecular targets for lithium in the brain could lead to the elucidation of the pathophysiology of bipolar disorder and the discovery of a new generation of mood stabilizers, which in turn may lead to improvements in the long-term outcome of this devastating illness (1).

scholarly journals Space-occupying cerebellar infarction: complications, treatment, and outcome

2013 ◽  
Vol 34 (5) ◽  
pp. E8 ◽  
Author(s):  
Hermann Neugebauer ◽  
Jens Witsch ◽  
Klaus Zweckberger ◽  
Eric Jüttler
Keyword(s):  
Treatment Strategies ◽  
Cerebellar Infarction ◽  
General Belief ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cerebellar Stroke ◽  
Brainstem Compression ◽  
Pressure Lowering ◽  
Life Threatening ◽  
Close Cooperation

Space-occupying brain edema is a frequent and one of the most dreaded complications in ischemic cerebellar stroke. Because the tight posterior fossa provides little compensating space, any space-occupying lesion can lead to life-threatening complications through brainstem compression or compression of the fourth ventricle and subsequent hydrocephalus, both of which may portend transtentorial/transforaminal herniation. Patients with large cerebellar infarcts should be treated and monitored very early on in an experienced stroke unit or (neuro)intensive care unit. The general treatment of ischemic cerebellar infarction does not differ from that of supratentorial ischemic strokes. Treatment strategies for space-occupying edema include pharmacological antiedema and intracranial pressure–lowering therapies, ventricular drainage by means of an extraventricular drain, and suboccipital decompressive surgery, with or without resection of necrotic tissue. Timely escalation of treatment is crucial and should be guided by clinical and neuroradiological rationales. Patients in a coma after hydrocephalus and/or local brainstem compression may also benefit from more aggressive surgical treatment, as long as the conditions are reversible. Contrary to the general belief that outcome in survivors of space-occupying cerebellar stroke is usually good, recent studies suggest that for many of these patients, the long-term outcome is not good. In particular, advanced age and additional brainstem infarction seem to be predictors for poor outcome. Further trials are necessary to investigate these findings systematically and provide better selection criteria to help guide decisions about surgical therapies, which should always be carried out in close cooperation among neurointensive care physicians, neurologists, and neurosurgeons.

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.

Impact of treatment strategies on long-term outcome of CTO patients

2020 ◽  
Vol 77 ◽  
pp. 97-104 ◽  
Author(s):  
Christian Roth ◽  
Georg Goliasch ◽  
Stefan Aschauer ◽  
Clemens Gangl ◽  
Mohamed Ayoub ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Term Outcome ◽  
Long Term Outcome
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