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The Modulation of Potassium Channels in the Smooth Muscle as a Therapeutic Strategy for Disorders of the Gastrointestinal Tract
Publication date: Available online 6 January 2016 Source:Advances in Protein Chemistry and Structural Biology Author(s): Diego Currò Alterations of smooth muscle contractility contribute to the pathophysiology of important functional gastrointestinal disorders (FGIDs) such as functional dyspepsia and irritable bowel syndrome. Consequently, drugs that decrease smooth muscle contractility are effective treatments for these diseases. Smooth muscle contraction is mainly triggered by Ca2+ influx through voltage-dependent channels located in the plasma membrane. Thus, the modulation of the membrane potential results in th...
Source: Advances in Protein Chemistry and Structural Biology - January 15, 2016 Category: Biochemistry Source Type: research

Targeting the Channel Activity of Viroporins
Publication date: Available online 7 January 2016 Source:Advances in Protein Chemistry and Structural Biology Author(s): Janet To, Wahyu Surya, Jaume Torres Since the discovery that certain small viral membrane proteins, collectively termed as viroporins, can permeabilize host cellular membranes and also behave as ion channels, attempts have been made to link this feature to specific biological roles. In parallel, most viroporins identified so far are virulence factors, and interest has focused toward the discovery of channel inhibitors that would have a therapeutic effect, or be used as research tools to underst...
Source: Advances in Protein Chemistry and Structural Biology - January 15, 2016 Category: Biochemistry Source Type: research

Proteostasis Maintenance of Cys-Loop Receptors
Publication date: Available online 22 December 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): Yan-Lin Fu, Ya-Juan Wang, Ting-Wei Mu The Cys-loop receptors play prominent roles in the nervous system. They include γ-aminobutyric acid type A receptors, nicotinic acetylcholine receptors, 5-hydroxytryptamine type-3 receptors, and glycine receptors. Proteostasis represents an optimal state of the cellular proteome in normal physiology. The proteostasis network regulates the folding, assembly, degradation, and trafficking of the Cys-loop receptors, ensuring their efficient functional cell s...
Source: Advances in Protein Chemistry and Structural Biology - December 25, 2015 Category: Biochemistry Source Type: research

Calcium-Activated Potassium Channels: Potential Target for Cardiovascular Diseases
Publication date: Available online 23 December 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): D.L. Dong, Y.L. Bai, B.Z. Cai Ca2+-activated K+ channels (KCa) are classified into three subtypes: big conductance (BKCa), intermediate conductance (IKCa), and small conductance (SKCa) KCa channels. The three types of KCa channels have distinct physiological or pathological functions in cardiovascular system. BKCa channels are mainly expressed in vascular smooth muscle cells (VSMCs) and inner mitochondrial membrane of cardiomyocytes, activation of BKCa channels in these locations results in v...
Source: Advances in Protein Chemistry and Structural Biology - December 25, 2015 Category: Biochemistry Source Type: research

Glutamatergic NMDA Receptor as Therapeutic Target for Depression
Publication date: Available online 17 December 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): Gislaine Z. Réus, Helena M. Abelaira, Talita Tuon, Stephanie E. Titus, Zuleide M. Ignácio, Ana Lúcia S. Rodrigues, João Quevedo Major depressive disorder (MDD) affects approximately 121 million individuals globally and poses a significant burden to the healthcare system. Around 50–60% of patients with MDD respond adequately to existing treatments that are primarily based on a monoaminergic system. However, the neurobiology of MDD has not been fully elucidated; therefore, it is p...
Source: Advances in Protein Chemistry and Structural Biology - December 18, 2015 Category: Biochemistry Source Type: research

Harnessing the Flow of Excitation: TRP, Voltage-Gated Na+, and Voltage-Gated Ca2+ Channels in Contemporary Medicine
Publication date: Available online 10 December 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): Roman V. Frolov, Matti Weckström Cellular signaling in both excitable and nonexcitable cells involves several classes of ion channel. Some of them are of minor importance, with very specialized roles in physiology, but here we concentrate on three major channel classes: TRP (transient receptor potential channels), voltage-gated sodium channels (Nav), and voltage-gated calcium channels (Cav). Here, we first propose a conceptual framework binding together all three classes of ion channels, a “...
Source: Advances in Protein Chemistry and Structural Biology - December 12, 2015 Category: Biochemistry Source Type: research

Ion Channels in Neurological Disorders
Publication date: Available online 28 November 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): Pravir Kumar, Dhiraj Kumar, Saurabh Kumar Jha, Niraj Kumar Jha, Rashmi K. Ambasta The convergent endeavors of the neuroscientist to establish a link between clinical neurology, genetics, loss of function of an important protein, and channelopathies behind neurological disorders are quite intriguing. Growing evidence reveals the impact of ion channels dysfunctioning in neurodegenerative disorders (NDDs). Many neurological/neuromuscular disorders, viz, Alzheimer's disease, Parkinson's disea...
Source: Advances in Protein Chemistry and Structural Biology - November 30, 2015 Category: Biochemistry Source Type: research

pH-Sensitive K+ Currents and Properties of K2P Channels in Murine Hippocampal Astrocytes
In conclusion, the assembly of astrocytic K+ channels allows tolerating short, transient acidification, and glial Kir4.1 and K2P channels can be considered promising new targets in brain diseases accompanied by pH shifts. (Source: Advances in Protein Chemistry and Structural Biology)
Source: Advances in Protein Chemistry and Structural Biology - November 30, 2015 Category: Biochemistry Source Type: research

Personalized Pharmacoperones for Lysosomal Storage Disorder: Approach for Next-Generation Treatment
Publication date: Available online 26 November 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): S.A. Syed Haneef, C. George Priya Doss Lysosomal storage disorders (LSDs) are a collection of inborn errors of metabolic disorders affected by mutations in lysosome functional genes, commonly acid hydrolases. From the past decades, many approaches like enzyme replacement therapy, substrate reduction therapy are followed to treat these conditions. However, all these approaches have their own limitations. Proof-of-concept studies on pharmacological chaperone therapy (PCT) is now transformed into ...
Source: Advances in Protein Chemistry and Structural Biology - November 28, 2015 Category: Biochemistry Source Type: research

AMPA Receptors as Therapeutic Targets for Neurological Disorders
Publication date: Available online 19 November 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): Kevin Lee, Lucy Goodman, Chantelle Fourie, Susan Schenk, Beulah Leitch, Johanna M. Montgomery Almost every neurological disease directly or indirectly affects synapse function in the brain. However, these diseases alter synapses through different mechanisms, ultimately resulting in altered synaptic transmission and/or plasticity. Glutamate is the major neurotransmitter that mediates excitatory synaptic transmission in the brain through activation of alpha-amino-3-hydroxy-5-methyl-4-isox...
Source: Advances in Protein Chemistry and Structural Biology - November 23, 2015 Category: Biochemistry Source Type: research

Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases
Publication date: Available online 21 November 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): Beatrice Mihaela Radu, Adela Banciu, Daniel Dumitru Banciu, Mihai Radu Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g....
Source: Advances in Protein Chemistry and Structural Biology - November 23, 2015 Category: Biochemistry Source Type: research

Role of von Willebrand Factor—A1 Domain Variants P1266L, H1268D, C1272R, and C1272F in VWD: A Molecular Modeling and Simulation Analysis Approach
Publication date: Available online 21 November 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): C. George Priya Doss, Shabana Kouser Ali von Willebrand disease (VWD) is an autosomal inherited disorder related to trauma-related bleeding in affected people. VWD results from deficiency of von Willebrand factor (VWF)—a glycoprotein involved in hemostasis and carrier for factor VIII (FVIII). Mutations in A1 domain of von Willebrand factor (VWD) gene are exceptionally polymorphic and associated with adhesion movement, clearance, and binding properties that could be interfaced with thrombosis....
Source: Advances in Protein Chemistry and Structural Biology - November 23, 2015 Category: Biochemistry Source Type: research

Molecular Dynamics: New Frontier in Personalized Medicine
Publication date: Available online 14 November 2015 Source:Advances in Protein Chemistry and Structural Biology Author(s): P. Sneha, C. George Priya Doss The field of drug discovery has witnessed infinite development over the last decade with the demand for discovery of novel efficient lead compounds. Although the development of novel compounds in this field has seen large failure, a breakthrough in this area might be the establishment of personalized medicine. The trend of personalized medicine has shown stupendous growth being a hot topic after the successful completion of Human Genome Project and 1000 genomes pi...
Source: Advances in Protein Chemistry and Structural Biology - November 17, 2015 Category: Biochemistry Source Type: research

Chapter Nine SHOPIN
Publication date: 2015 Source:Advances in Protein Chemistry and Structural Biology, Volume 101 Author(s): Kire Trivodaliev, Slobodan Kalajdziski, Ilinka Ivanoska, Biljana Risteska Stojkoska, Ljupco Kocarev Protein interaction networks (PINs) are argued to be the richest source of hidden knowledge of the intrinsic physical and/or functional meanings of the involved proteins. We propose a novel method for computational protein function prediction based on semantic homogeneity optimization in PIN (SHOPIN). The SHOPIN method creates graph representations of the PIN augmented by inclusion of the semantics of the p...
Source: Advances in Protein Chemistry and Structural Biology - November 15, 2015 Category: Biochemistry Source Type: research

Chapter Eight Human Papillomavirus Vaccine
Publication date: 2015 Source:Advances in Protein Chemistry and Structural Biology, Volume 101 Author(s): Donatella Panatto, Daniela Amicizia, Nicola Luigi Bragazzi, Emanuela Rizzitelli, Daniela Tramalloni, Ivana Valle, Roberto Gasparini Human Papillomavirus (HPV) is a widely distributed and common virus, that causes benign lesions (such as warts and papillomas) but, if not cleared, can lead to malignant lesions as well, such as intraepithelial lesions and neoplasia. An extensive body of researches has demonstrated that E1 and E2 are involved in viral transcription and replication, E5, E6, and E7 act as o...
Source: Advances in Protein Chemistry and Structural Biology - November 15, 2015 Category: Biochemistry Source Type: research