scholarly journals GABAA receptors: structure, function, pharmacology, and related disorders

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Amr Ghit ◽  
Dina Assal ◽  
Ahmed S. Al-Shami ◽  
Diaa Eldin E. Hussein
Keyword(s):  
Ion Channel ◽  
Chloride Ion ◽  
Structural Heterogeneity ◽  
Normal Brain ◽  
Main Body ◽  
Inhibitory Neurotransmitter ◽  
Therapeutic Implications ◽  
Receptor Isoforms ◽  
Wide Range ◽  
Normal Brain Function

Abstract Background γ-Aminobutyric acid sub-type A receptors (GABAARs) are the most prominent inhibitory neurotransmitter receptors in the CNS. They are a family of ligand-gated ion channel with significant physiological and therapeutic implications. Main body GABAARs are heteropentamers formed from a selection of 19 subunits: six α (alpha1-6), three β (beta1-3), three γ (gamma1-3), three ρ (rho1-3), and one each of the δ (delta), ε (epsilon), π (pi), and θ (theta) which result in the production of a considerable number of receptor isoforms. Each isoform exhibits distinct pharmacological and physiological properties. However, the majority of GABAARs are composed of two α subunits, two β subunits, and one γ subunit arranged as γ2β2α1β2α1 counterclockwise around the center. The mature receptor has a central chloride ion channel gated by GABA neurotransmitter and modulated by a variety of different drugs. Changes in GABA synthesis or release may have a significant effect on normal brain function. Furthermore, The molecular interactions and pharmacological effects caused by drugs are extremely complex. This is due to the structural heterogeneity of the receptors, and the existence of multiple allosteric binding sites as well as a wide range of ligands that can bind to them. Notably, dysfunction of the GABAergic system contributes to the development of several diseases. Therefore, understanding the relationship between GABAA receptor deficits and CNS disorders thus has a significant impact on the discovery of disease pathogenesis and drug development. Conclusion To date, few reviews have discussed GABAA receptors in detail. Accordingly, this review aims to summarize the current understanding of the structural, physiological, and pharmacological properties of GABAARs, as well as shedding light on the most common associated disorders.

A Survey on Detection and Classification of Brain Tumor Using Image Processing Techniques

2020 ◽  
pp. 967-973
Author(s):  
V. Deepika ◽  
T. Rajasenbagam
Keyword(s):  
Image Processing ◽  
Brain Tumor ◽  
Soft Tissues ◽  
Tumor Detection ◽  
Tumor Classification ◽  
Normal Brain ◽  
Image Processing Techniques ◽  
Normal Brain Function ◽  
Processing Techniques ◽  
The Brain

A brain tumor is an uncontrolled growth of abnormal brain tissue that can interfere with normal brain function. Although various methods have been developed for brain tumor classification, tumor detection and multiclass classification remain challenging due to the complex characteristics of the brain tumor. Brain tumor detection and classification are one of the most challenging and time-consuming tasks in the processing of medical images. MRI (Magnetic Resonance Imaging) is a visual imaging technique, which provides a information about the soft tissues of the human body, which helps identify the brain tumor. Proper diagnosis can prevent a patient's health to some extent. This paper presents a review of various detection and classification methods for brain tumor classification using image processing techniques.

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

Impacts of Iron Metabolism Dysregulation on Alzheimer’s Disease

2021 ◽  
Vol 80 (4) ◽  
pp. 1439-1450
Author(s):  
Najla Jouini ◽  
Zakaria Saied ◽  
Samia Ben Sassi ◽  
Fatma Nebli ◽  
Taieb Messaoud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant System ◽  
Plasma Concentrations ◽  
Normal Brain ◽  
Cognitively Normal ◽  
Iron Trafficking ◽  
Major Species ◽  
Normal Brain Function ◽  
Calcium Magnesium

Background: Iron plays an important role in maintaining cell survival, with normal iron trafficking known to be regulated by the ceruloplasmin-transferrin (Cp-Tf) antioxidant system. Disruption to this system is thought to be detrimental to normal brain function. Objective: To determine whether an imbalance of iron and the proteins involved in its metabolism (ceruloplasmin and transferrin) are linked to Alzheimer’s disease (AD) and to the expression of amyloid-beta (Aβ) peptide 1–42 (Aβ1–42), which is a major species of Aβ, and the most toxic. Methods: We evaluated the concentrations of iron, calcium, magnesium, and Aβ1–42 in the cerebrospinal fluid (CSF) of patients with AD and cognitively normal controls. Correlations between the components of the Cp-Tf antioxidant system in plasma were studied to determine the role of peripheral blood in the onset and/or development of AD. We used commercial ELISA immunoassays to measure Aβ1–42, immunoturbidimetry to quantify ceruloplasmin and transferrin, and colorimetry to quantify iron, calcium, and magnesium. Results: We found that the AD group had lower CSF concentrations of Aβ1–42 (p < 0.001) and calcium (p < 0.001), but a higher CSF concentration of iron (p < 0.001). Significantly lower plasma concentrations of ceruloplasmin (p = 0.003), transferrin (mean, p < 0.001), and iron (p < 0.001) were observed in the AD group than in cognitively normal adults. Moreover, we found a strong interdependence between most of these components. Conclusion: Iron dyshomeostasis has a crucial role in the onset of AD and/or its development. Correcting metal misdistribution is an appealing therapeutic strategy for AD.

scholarly journals Potential predictors of severe cardiovascular involvement in Marfan syndrome: the emphasized role of genotype–phenotype correlations in improving risk stratification—a literature review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Roland Stengl ◽  
Bence Ágg ◽  
Miklós Pólos ◽  
Gábor Mátyás ◽  
Gábor Szabó ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Marfan Syndrome ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Connective Tissue Disorder ◽  
Main Body ◽  
Wide Range ◽  
Stratification System ◽  
Genetically Determined ◽  
Aortic Dissections

Abstract Background Marfan syndrome (MFS) is a genetically determined systemic connective tissue disorder, caused by a mutation in the FBN1 gene. In MFS mainly the cardiovascular, musculoskeletal and ocular systems are affected. The most dangerous manifestation of MFS is aortic dissection, which needs to be prevented by a prophylactic aortic root replacement. Main body The indication criteria for the prophylactic procedure is currently based on aortic diameter, however aortic dissections below the threshold defined in the guidelines have been reported, highlighting the need for a more accurate risk stratification system to predict the occurrence of aortic complications. The aim of this review is to present the current knowledge on the possible predictors of severe cardiovascular manifestations in MFS patients, demonstrating the wide range of molecular and radiological differences between people with MFS and healthy individuals, and more importantly between MFS patients with and without advanced aortic manifestations. These differences originating from the underlying common molecular pathological processes can be assessed by laboratory (e.g. genetic testing) and imaging techniques to serve as biomarkers of severe aortic involvement. In this review we paid special attention to the rapidly expanding field of genotype–phenotype correlations for aortic features as by collecting and presenting the ever growing number of correlations, future perspectives for risk stratification can be outlined. Conclusions Data on promising biomarkers of severe aortic complications of MFS have been accumulating steadily. However, more unifying studies are required to further evaluate the applicability of the discussed predictors with the aim of improving the risk stratification and therefore the life expectancy and quality of life of MFS patients.

scholarly journals P149 The intracellular chloride channel 4 (CLIC4) plays an important role in systemic sclerosis fibroblast activation

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Christopher Wasson ◽  
Rebecca Ross ◽  
Ruth Morton ◽  
Jamel Mankouri ◽  
Francesco Del Galdo
Keyword(s):  
Systemic Sclerosis ◽  
Ion Channel ◽  
Smooth Muscle Actin ◽  
Chloride Ion ◽  
Dermal Fibroblasts ◽  
Cancer Associated Fibroblasts ◽  
Alpha Smooth Muscle Actin ◽  
Direct Role ◽  
Fibroblast Activation ◽  
Intracellular Chloride

Abstract Background/Aims  The intracellular chloride ion channel CLIC4 mediates the activation of cancer associated fibroblasts. Interestingly, systemic sclerosis (SSc) fibroblasts display a number of similar properties to cancer associated fibroblasts. Tissue fibrosis in SSc is driven by active fibroblasts (myofibroblasts). Therefore in this study we investigated the role of CLIC4 in SSc fibroblast activation. Methods  Dermal fibroblasts were obtained from full thickness skin biopsies from SSc patients (early-diffuse). RNA and protein were collected from the fibroblasts and CLIC4 transcript and protein levels were assessed by qPCR and western blot. SSc patient fibroblasts were treated with the chloride ion channel inhibitors NPPB and IAA-94. Results  CLIC4 was found to be expressed at significantly higher levels in SSc patients fibroblasts compared to healthy controls, at both the transcript (3.7 fold) and protein (1.7 fold) levels. Inhibition of the TGF-β signalling pathway led to reduced CLIC4 expression in SSc fibroblasts, confirming this pathway as the main driver of CLIC4 expression. Finally, treatment of SSc fibroblasts with small molecule inhibitors that target the channel led to reduced expression of the myofibroblast markers collagen type 1 and alpha-smooth muscle actin, suggesting a direct role for CLIC4 in SSc associated skin fibrosis. Conclusion  We have identified a novel role for CLIC4 in SSc myofibroblast activation, which further strengthen the similarities between SSc fibroblasts and cancer associated fibroblasts. Furthermore this study highlights this channel as a novel target for therapeutic intervention. Disclosure  C. Wasson: None. R. Ross: None. R. Morton: None. J. Mankouri: None. F. Del Galdo: None.

scholarly journals Cranioplasty Sinking Should Affect Normal Brain Function Mimicking Other Neurologic Illness: Fig 1.

2012 ◽  
Vol 33 (4) ◽  
pp. e65-e65
Author(s):  
M. del Mar Carmona Abellán ◽  
M. Murie Fernández ◽  
P. Esteve Belloch
Keyword(s):  
Brain Function ◽  
Normal Brain ◽  
Normal Brain Function

scholarly journals Membrane Currents in Airway Smooth Muscle: Mechanisms and Therapeutic Implications

1997 ◽  
Vol 4 (1) ◽  
pp. 13-20
Author(s):  
Luke J Janssen
Keyword(s):  
Smooth Muscle ◽  
Ion Channels ◽  
Calcium Channels ◽  
Airway Smooth Muscle ◽  
Calcium Ion ◽  
Membrane Conductance ◽  
Chloride Ion ◽  
Potassium Ion Channels ◽  
Therapeutic Implications ◽  
Transient Activation

Electrophysiological and pharmacological techniques were used to characterize the membrane conductance changes underlying spasmogen-evoked depolarization in airway smooth muscle (ASM). Changes included a transient activation of chloride ion channels and prolonged suppression of potassium ion channels; both changes are triggered by release of internally sequestered calcium ion and in turn cause opening of voltage-dependent calcium channels. The resultant influx of calcium ions contributes to contraction as well as to refilling of the internal calcium ion pool. Bronchodilators, on the other hand, act in part through activation of potassium channels, with consequent closure of calcium channels. The tools used to study ion channels in ASM are described, and the investigations of the roles of ion channels in ASM physiology (autacoid-evoked depolarization and hyperpolarization) and pathophysiology (airway hyperresponsiveness) are summarized. Finally, how the relationship between ion channels and ASM function/dysfunction may relate to the treatment of asthma and related breathing disorders is discussed.

scholarly journals Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172884 ◽  
Author(s):  
Julia Pollak ◽  
Karan G. Rai ◽  
Cory C. Funk ◽  
Sonali Arora ◽  
Eunjee Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ion Channel ◽  
Expression Patterns ◽  
Glioblastoma Stem Cells ◽  
Therapeutic Implications ◽  
Channel Expression

THE INSULA: ISLAND OF REIL

2015 ◽  
Vol 86 (11) ◽  
pp. e4.155-e4
Author(s):  
Ray Wynford-Thomas ◽  
Rob Powell
Keyword(s):  
Speech Processing ◽  
Brain Function ◽  
Insular Cortex ◽  
Normal Brain ◽  
Temporal Epilepsy ◽  
Normal Brain Function ◽  
Temporal Structures ◽  
Hypermotor Seizures ◽  
Posterior Insula ◽  
As Effects

Just as ‘no man is an island’, despite its misleading name, the insula is not an island. Sitting deeply within the cerebrum, the insular cortex and its connections play an important role in both normal brain function and seizure generation. Stimulating specific areas of the insula can produce somatosensory, viscerosensory, somatomotor and visceroautonomic symptoms, as well as effects on speech processing and pain. Insular onset seizures are rare, but may mimic both temporal and extra-temporal epilepsy and if not recognised, may lead to failure of epilepsy surgery. We therefore highlight the semiology of insular epilepsy by discussing three cases with different auras. Insular onset seizures can broadly be divided into three main types both anatomically and according to seizure semiology:1. Seizures originating in the antero-inferior insula present with laryngeal constriction, along with visceral and gustatory auras (similar to those originating in medial temporal structures).2. Antero-superior onset seizures can have a silent onset, but tend to propagate rapidly to motor areas causing focal motor or hypermotor seizures.3. Seizures originating in the posterior insula present with contralateral sensory symptoms.

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