scholarly journals Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels

2021 ◽  
Vol 14 ◽  
Author(s):  
Deepanjali Dwivedi ◽  
Upinder S. Bhalla
Keyword(s):  
Ion Channels ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Brain Regions ◽  
Channel Activity ◽  
Current Review ◽  
Cellular Excitability ◽  
M Channels ◽  
Neuronal Functions

SK, HCN, and M channels are medium afterhyperpolarization (mAHP)-mediating ion channels. The three channels co-express in various brain regions, and their collective action strongly influences cellular excitability. However, significant diversity exists in the expression of channel isoforms in distinct brain regions and various subcellular compartments, which contributes to an equally diverse set of specific neuronal functions. The current review emphasizes the collective behavior of the three classes of mAHP channels and discusses how these channels function together although they play specialized roles. We discuss the biophysical properties of these channels, signaling pathways that influence the activity of the three mAHP channels, various chemical modulators that alter channel activity and their therapeutic potential in treating various neurological anomalies. Additionally, we discuss the role of mAHP channels in the pathophysiology of various neurological diseases and how their modulation can alleviate some of the symptoms.

scholarly journals Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

2021 ◽  
Vol 18 (8) ◽  
pp. 3993
Author(s):  
Aaron M. Farrelly ◽  
Styliani Vlachou ◽  
Konstantinos Grintzalis
Keyword(s):  
Therapeutic Potential ◽  
Significant Proportion ◽  
Future Research ◽  
Specific Reference ◽  
Undesirable Side Effect ◽  
Treatment Resistant ◽  
Current Review ◽  
Epilepsy Treatment ◽  
Clinical Environments

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.

scholarly journals Role and Therapeutic Potential of Melatonin in the Central Nervous System and Cancers

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1567
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Dark Phase ◽  
Anti Inflammatory ◽  
The Impact

Melatonin (MLT) is a powerful chronobiotic hormone that controls a multitude of circadian rhythms at several levels and, in recent times, has garnered considerable attention both from academia and industry. In several studies, MLT has been discussed as a potent neuroprotectant, anti-apoptotic, anti-inflammatory, and antioxidative agent with no serious undesired side effects. These characteristics raise hopes that it could be used in humans for central nervous system (CNS)-related disorders. MLT is mainly secreted in the mammalian pineal gland during the dark phase, and it is associated with circadian rhythms. However, the production of MLT is not only restricted to the pineal gland; it also occurs in the retina, Harderian glands, gut, ovary, testes, bone marrow, and lens. Although most studies are limited to investigating the role of MLT in the CNS and related disorders, we explored a considerable amount of the existing literature. The objectives of this comprehensive review were to evaluate the impact of MLT on the CNS from the published literature, specifically to address the biological functions and potential mechanism of action of MLT in the CNS. We document the effectiveness of MLT in various animal models of brain injury and its curative effects in humans. Furthermore, this review discusses the synthesis, biology, function, and role of MLT in brain damage, and as a neuroprotective, antioxidative, anti-inflammatory, and anticancer agent through a collection of experimental evidence. Finally, it focuses on the effect of MLT on several neurological diseases, particularly CNS-related injuries.

Role of the glucose-dependent insulinotropic polypeptide and its receptor in the central nervous system: therapeutic potential in neurological diseases

2010 ◽  
Vol 21 (5-6) ◽  
pp. 394-408 ◽  
Author(s):  
Cláudia P. Figueiredo ◽  
Fabrício A. Pamplona ◽  
Tânia L. Mazzuco ◽  
Aderbal S. Aguiar ◽  
Roger Walz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
The Central Nervous System

scholarly journals Activity and Function of the PRMT8 Protein Arginine Methyltransferase in Neurons

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1132
Author(s):  
Rui Dong ◽  
Xuejun Li ◽  
Kwok-On Lai
Keyword(s):  
Potential Role ◽  
Neurological Diseases ◽  
Structural Features ◽  
Protein Arginine Methyltransferases ◽  
Synapse Maturation ◽  
Membrane Bound ◽  
And Function ◽  
Neuronal Functions ◽  
Mammalian Protein

Among the nine mammalian protein arginine methyltransferases (PRMTs), PRMT8 is unusual because it has restricted expression in the nervous system and is the only membrane-bound PRMT. Emerging studies have demonstrated that this enzyme plays multifaceted roles in diverse processes in neurons. Here we will summarize the unique structural features of PRMT8 and describe how it participates in various neuronal functions such as dendritic growth, synapse maturation, and synaptic plasticity. Recent evidence suggesting the potential role of PRMT8 function in neurological diseases will also be discussed.

scholarly journals The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Mohammad Rafi Khezri ◽  
Reza Varzandeh ◽  
Morteza Ghasemnejad-Berenji
Keyword(s):  
Signaling Pathway ◽  
Distress Syndrome ◽  
Therapeutic Potential ◽  
Coagulation Factors ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Current Review ◽  
Probable Role ◽  
Intracellular Pathway

AbstractCoronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is associated with a high mortality rate. The majority of deaths in this disease are caused by ARDS (acute respiratory distress syndrome) followed by cytokine storm and coagulation complications. Although alterations in the level of the number of coagulation factors have been detected in samples from COVID-19 patients, the direct molecular mechanism which has been involved in this pathologic process has not been explored yet. The PI3K/AKT signaling pathway is an intracellular pathway which plays a central role in cell survival. Also, in recent years the association between this pathway and coagulopathies has been well clarified. Therefore, based on the evidence on over-activity of the PI3K/AKT signaling pathway in SARS-CoV-2 infection, in the current review, the probable role of this cellular pathway as a therapeutic target for the prevention of coagulation complications in patients with COVID-19 is discussed.

The Therapeutic Potential of miR-7 in Cancers

2019 ◽  
Vol 19 (20) ◽  
pp. 1707-1716 ◽  
Author(s):  
Miao Li ◽  
Meng Pan ◽  
Chengzhong You ◽  
Jun Dou
Keyword(s):  
Tumor Suppressor ◽  
Future Study ◽  
Therapeutic Potential ◽  
Biological Processes ◽  
Multiple Cancer ◽  
Current Review ◽  
Cancer Types ◽  
The Relationship ◽  
Potent Tumor

MiRNAs play an important role in cancers. As a potent tumor suppressor, miRNA-7(miR-7) has been demonstrated to inhibit the diverse fundamental biological processes in multiple cancer types including initiation, growth and metastasis by targeting a number of molecules and signaling pathways. This current review summarizes and discusses the relationship between miR-7 and cancers and the therapeutic potential of miR-7 in cancers. It may provide new integrative understanding for future study on the role of miR-7 in cancers.

scholarly journals Neuromodulation with transcranial focused ultrasound

2018 ◽  
Vol 44 (2) ◽  
pp. E14 ◽  
Author(s):  
Jan Kubanek
Keyword(s):  
Focused Ultrasound ◽  
Brain Regions ◽  
Stimulation Parameters ◽  
Cellular Excitability ◽  
Psychiatric Conditions ◽  
Specific Stimulation ◽  
Future Work ◽  
The Brain ◽  
Transcranial Focused Ultrasound

The understanding of brain function and the capacity to treat neurological and psychiatric disorders rest on the ability to intervene in neuronal activity in specific brain circuits. Current methods of neuromodulation incur a tradeoff between spatial focus and the level of invasiveness. Transcranial focused ultrasound (FUS) is emerging as a neuromodulation approach that combines noninvasiveness with focus that can be relatively sharp even in regions deep in the brain. This may enable studies of the causal role of specific brain regions in specific behaviors and behavioral disorders. In addition to causal brain mapping, the spatial focus of FUS opens new avenues for treatments of neurological and psychiatric conditions. This review introduces existing and emerging FUS applications in neuromodulation, discusses the mechanisms of FUS effects on cellular excitability, considers the effects of specific stimulation parameters, and lays out the directions for future work.

scholarly journals Ion channels in cancer: future perspectives and clinical potential

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130108 ◽  
Author(s):  
Florian Lang ◽  
Christos Stournaras
Keyword(s):  
Ion Channels ◽  
Cell Survival ◽  
Tumour Cell ◽  
Tumour Growth ◽  
Therapeutic Potential ◽  
Short Review ◽  
Therapy Resistance ◽  
Tumour Cells ◽  
Anion Channels

Ion transport across the cell membrane mediated by channels and carriers participate in the regulation of tumour cell survival, death and motility. Moreover, the altered regulation of channels and carriers is part of neoplastic transformation. Experimental modification of channel and transporter activity impacts tumour cell survival, proliferation, malignant progression, invasive behaviour or therapy resistance of tumour cells. A wide variety of distinct Ca 2+ permeable channels, K + channels, Na + channels and anion channels have been implicated in tumour growth and metastasis. Further experimental information is, however, needed to define the specific role of individual channel isoforms critically important for malignancy. Compelling experimental evidence supports the assumption that the pharmacological inhibition of ion channels or their regulators may be attractive targets to counteract tumour growth, prevent metastasis and overcome therapy resistance of tumour cells. This short review discusses the role of Ca 2+ permeable channels, K + channels, Na + channels and anion channels in tumour growth and metastasis and the therapeutic potential of respective inhibitors.

scholarly journals Astrocytic IP3Rs: Beyond IP3R2

2021 ◽  
Vol 15 ◽  
Author(s):  
Mark W. Sherwood ◽  
Misa Arizono ◽  
Aude Panatier ◽  
Katsuhiko Mikoshiba ◽  
Stéphane H. R. Oliet
Keyword(s):  
Synaptic Plasticity ◽  
G Protein Coupled Receptors ◽  
Release Channel ◽  
Physiological Conditions ◽  
Current Review ◽  
Intracellular Ca ◽  
Neuronal Functions ◽  
G Protein Coupled ◽  
Distinct Distribution

Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g., glutamate, glycine, D-serine, ATP). To sense diverse input, astrocytes express a plethora of G-protein coupled receptors, which couple, via Gi/o and Gq, to the intracellular Ca2+ release channel IP3-receptor (IP3R). Indeed, manipulating astrocytic IP3R-Ca2+ signaling is highly consequential at the network and behavioral level: Depleting IP3R subtype 2 (IP3R2) results in reduced GPCR-Ca2+ signaling and impaired synaptic plasticity; enhancing IP3R-Ca2+ signaling affects cognitive functions such as learning and memory, sleep, and mood. However, as a result of discrepancies in the literature, the role of GPCR-IP3R-Ca2+ signaling, especially under physiological conditions, remains inconclusive. One primary reason for this could be that IP3R2 has been used to represent all astrocytic IP3Rs, including IP3R1 and IP3R3. Indeed, IP3R1 and IP3R3 are unique Ca2+ channels in their own right; they have unique biophysical properties, often display distinct distribution, and are differentially regulated. As a result, they mediate different physiological roles to IP3R2. Thus, these additional channels promise to enrich the diversity of spatiotemporal Ca2+ dynamics and provide unique opportunities for integrating neuronal input and modulating astrocyte–neuron communication. The current review weighs evidence supporting the existence of multiple astrocytic-IP3R isoforms, summarizes distinct sub-type specific properties that shape spatiotemporal Ca2+ dynamics. We also discuss existing experimental tools and future refinements to better recapitulate the endogenous activities of each IP3R isoform.

Contributions of Bile Acids to Gastrointestinal Physiology as Receptor Agonists and Modifiers of Ion Channels

2021 ◽  
Author(s):  
Stephen Joseph Keely ◽  
Andreacarola Urso ◽  
Alexandr V Ilyaskin ◽  
Christoph Korbmacher ◽  
Nigel W Bunnett ◽  
...  
Keyword(s):  
Ion Channels ◽  
Bile Acids ◽  
Intestinal Motility ◽  
Molecular Mechanisms ◽  
Epithelial Transport ◽  
Therapeutic Potential ◽  
Gastrointestinal Diseases ◽  
Gastrointestinal Physiology ◽  
The Past ◽  
Current Review

BAs are known to be important regulators of intestinal motility and epithelial fluid and electrolyte transport. Over the past two decades, significant advances in identifying and characterizing the receptors, transporters, and ion channels targeted by bile acids (BAs) has led to exciting new insights into the molecular mechanisms involved in these processes. Our appreciation of BAs, their receptors and BA-modulated ion channels as potential targets for the development of new approaches to treat intestinal motility and transport disorders is increasing. In the current review, we aim to summarize recent advances in our knowledge of the different BA receptors and BA-modulated ion channels present in the gastrointestinal system. We discuss how they regulate motility and epithelial transport, their roles in pathogenesis and their therapeutic potential in a range of gastrointestinal diseases.

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