scholarly journals Ghrelin-Mediated Regeneration and Plasticity After Nervous System Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Irina Stoyanova ◽  
David Lutz
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Neuronal Plasticity ◽  
Therapeutic Potential ◽  
Synaptic Activity ◽  
Systemic Effects ◽  
Metabolic Processes ◽  
Vast Number ◽  
Neuronal Circuitry

The nervous system is highly vulnerable to different factors which may cause injury followed by an acute or chronic neurodegeneration. Injury involves a loss of extracellular matrix integrity, neuronal circuitry disintegration, and impairment of synaptic activity and plasticity. Application of pleiotropic molecules initiating extracellular matrix reorganization and stimulating neuronal plasticity could prevent propagation of the degeneration into the tissue surrounding the injury. To find an omnipotent therapeutic molecule, however, seems to be a fairly ambitious task, given the complex demands of the regenerating nervous system that need to be fulfilled. Among the vast number of candidates examined so far, the neuropeptide and hormone ghrelin holds within a very promising therapeutic potential with its ability to cross the blood-brain barrier, to balance metabolic processes, and to stimulate neurorepair and neuroactivity. Compared with its well-established systemic effects in treatment of metabolism-related disorders, the therapeutic potential of ghrelin on neuroregeneration upon injury has received lesser appreciation though. Here, we discuss emerging concepts of ghrelin as an omnipotent player unleashing developmentally related molecular cues and morphogenic cascades, which could attenuate and/or counteract acute and chronic neurodegeneration.

scholarly journals Exercise-Associated Pathways as Novel Neuroprotectants Against CNS Aging and Alzheimer’s Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 373-373
Author(s):  
Constanza Cortes
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Transgenic Mouse ◽  
Therapeutic Potential ◽  
Bioactive Molecules ◽  
Systemic Effects ◽  
Master Regulator ◽  
Post Exercise

Abstract Skeletal muscle has recently arisen as a novel regulators of Central Nervous System (CNS) function and aging, secreting bioactive molecules known as myokines with proteostasis and metabolism-modifying functions in targeted tissues. We have recently generated a novel transgenic mouse with enhanced muscle proteostasis via moderate overexpression of Transcription Factor E-B (TFEB), a powerful master regulator of cellular clearance and proteostasis. We have discovered that the resulting enhanced skeletal muscle proteostasis function can significantly ameliorate proteotoxicity in the aging CNS and improve cognition and memory in aging mice. These neuroprotective benefits are markedly reminiscent of those observed in the aging CNS post-exercise, suggesting enhancing muscle proteostasis may be sufficient to replicate the local and systemic effects of exercise. Identification of pathways regulating crosstalk between skeletal muscle and CNS may yield targets with high therapeutic potential for diseases of the aging CNS.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

The Therapeutic Potential of Chemokines in the Treatment of Chemotherapy- Induced Peripheral Neuropathy

2020 ◽  
Vol 21 (3) ◽  
pp. 288-301 ◽  
Author(s):  
Lin Zhou ◽  
Luyao Ao ◽  
Yunyi Yan ◽  
Wanting Li ◽  
Anqi Ye ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Immune System ◽  
Peripheral Neuropathy ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Chemotherapeutic Agents ◽  
Cell Trafficking ◽  
Mediated Communication ◽  
Novel Therapeutic Strategies

Background: Some of the current challenges and complications of cancer therapy are chemotherapy- induced peripheral neuropathy (CIPN) and the neuropathic pain that are associated with this condition. Many major chemotherapeutic agents can cause neurotoxicity, significantly modulate the immune system and are always accompanied by various adverse effects. Recent evidence suggests that cross-talk occurs between the nervous system and the immune system during treatment with chemotherapeutic agents; thus, an emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN, as demonstrated by the upregulation of chemokines. Chemokines were originally identified as regulators of peripheral immune cell trafficking, and chemokines are also expressed on neurons and glial cells in the central nervous system. Objective: In this review, we collected evidence demonstrating that chemokines are potential mediators and contributors to pain signalling in CIPN. The expression of chemokines and their receptors, such as CX3CL1/CX3CR1, CCL2/CCR2, CXCL1/CXCR2, CXCL12/CXCR4 and CCL3/CCR5, is altered in the pathological conditions of CIPN, and chemokine receptor antagonists attenuate neuropathic pain behaviour. Conclusion: By understanding the mechanisms of chemokine-mediated communication, we may reveal chemokine targets that can be used as novel therapeutic strategies for the treatment of CIPN.

Ethanolamine: A Potential Promoiety with Additional Effects in the Brain

2020 ◽  
Vol 19 ◽  
Author(s):  
Asfree Gwanyanya ◽  
Christie Nicole Godsmark ◽  
Roisin Kelly-Laubscher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Design ◽  
Cell Signaling ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
The Central Nervous System ◽  
Bioactive Molecule ◽  
Positive Functions ◽  
The Brain

Abstract: Ethanolamine is a bioactive molecule found in several cells, including those in the central nervous system (CNS). In the brain, ethanolamine and ethanolamine-related molecules have emerged as prodrug moieties that can promote drug movement across the blood-brain barrier. This improvement in the ability to target drugs to the brain may also mean that in the process ethanolamine concentrations in the brain are increased enough for ethanolamine to exert its own neurological ac-tions. Ethanolamine and its associated products have various positive functions ranging from cell signaling to molecular storage, and alterations in their levels have been linked to neurodegenerative conditions such as Alzheimer’s disease. This mini-review focuses on the effects of ethanolamine in the CNS and highlights the possible implications of these effects for drug design.

BioSignal modelling for prediction of cardiac diseases using intra group selection method

2021 ◽  
Vol 15 (1) ◽  
pp. 151-160
Author(s):  
Hemant P. Kasturiwale ◽  
Sujata N. Kale
Keyword(s):  
Machine Learning ◽  
Nervous System ◽  
Random Forest ◽  
Normal Sinus Rhythm ◽  
Heart Defects ◽  
Support Vector ◽  
Autonomous Nervous System ◽  
Cardiac Diseases ◽  
Vast Number ◽  
Proposed Model

The Autonomous Nervous System (ANS) controls the nervous system and Heart Rate Variability (HRV) can be used as a diagnostic tool to diagnose heart defects. HRV can be classified into linear and nonlinear HRV indices which are used mostly to measure the efficiency of the model. For prediction of cardiac diseases, the selection and extraction features of machine learning model are effective. The available model used till date is based on HRV indices to predict the cardiac diseases accurately. The model could hardly throw light on specifics of indices, selection process and stability of the model. The proposed model is developed considering all facet electrocardiogram amplitude (ECG), frequency components, sampling frequency, extraction methods and acquisition techniques. The machine learning based model and its performance shall be tested using the standard BioSignal method, both on the data available and on the data obtained by the author. This is unique model developed by considering the vast number of mixtures sets and more than four complex cardiac classes. The statistical analysis is performed on a variety of databases such as MIT/BIH Normal Sinus Rhythm (NSR), MIT/BIH Arrhythmia (AR) and MIT/BIH Atrial Fibrillation (AF) and Peripheral Pule Analyser using feature compatibility techniques. The classifiers are trained for prediction with approximately 40000 sets of parameters. The proposed model reaches an average accuracy of 97.87 percent and is sensitive and précised. The best features are chosen from the different HRV features that will be used for classification. The present model was checked under all possible subject scenarios, such as the raw database and the non-ECG signal. In this sense, robustness is defined not only by the specificity parameter, but also by other measuring output parameters. Support Vector Machine (SVM), K-nearest Neighbour (KNN), Ensemble Adaboost (EAB) with Random Forest (RF) are tested in a 5% higher precision band and a lower band configuration. The Random Forest has produced better results, and its robustness has been established.

scholarly journals Neurobiology of Cancer: Introduction of New Drugs in the Treatment and Prevention of Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 6115
Author(s):  
Boris Mravec
Keyword(s):  
Nervous System ◽  
Animal Models ◽  
Therapeutic Potential ◽  
Clinical Findings ◽  
New Drugs ◽  
Adrenergic Signaling ◽  
Treatment And Prevention ◽  
Oncological Patients ◽  
Cancer Initiation ◽  
Prevention Of Cancer

Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the course of cancer in oncological patients. Moreover, it has been shown that reducing adrenergic signaling might also reduce the incidence of cancer in animal models, as well as in humans. However, even if many experimental and clinical findings have confirmed the preventive and therapeutic potential of drugs that reduce the stimulatory effect of the nervous system on processes related to cancer initiation and progression, several questions remain unanswered. Therefore, the aim of this review is to critically evaluate the efficiency of these drugs and to discuss questions that need to be answered before their introduction into conventional cancer treatment and prevention.

scholarly journals Central nervous system delivery of molecules across the blood-brain barrier

2021 ◽  
pp. 104952
Author(s):  
Fabien Gosselet ◽  
Rodrigo Azevedo Loiola ◽  
Anna Roig ◽  
Anna Rosell ◽  
Maxime Culot
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain
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