Toxins for decoding interface selectivity in nicotinic acetylcholine receptors

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that play crucial roles in neurotransmission and regulate complex processes in brain functions, including anxiety, learning and memory, food intake, drug addiction, cognition and nociception. To perform these and other functions, a diverse array of nAChR subtypes are generated by homomeric or heteromeric assembly of 17 homologous nAChR subunits. Agonists, acetylcholine and nicotine, bind to the interface formed between two α subunits and between α and non-α subunits to activate the nAChR and allow cation influx. The diversity of subunit interfaces determines the channel properties, the responses to different agonists/antagonists, desensitization and downstream signaling and thus, define specialized properties and functions. Over the last several decades, snake venom neurotoxins have contributed to the purification, localization and characterization of molecular details of various nAChRs. Utkin et al. have described the purification and characterization of α-bungarotoxins, a novel class of neurotoxins in a recent paper published in the Biochemical Journal [Biochem. J. (2019) 476, 1285–1302]. These toxins from Bungarus candidus venom preferably bind to α– site with two orders of magnitude higher affinity compared with α– or α– sites. The subtle changes in the structure of α-bungarotoxins led to variation in interface selecti...
Source: Biochemical Journal - Category: Biochemistry Authors: Tags: Commentaries Source Type: research

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Purpose of review To review the literature and provide a guide to assessing patients with problematic interactive media use (PIMU). Recent findings 0.3–1.0% of the world population meets criteria for internet gaming disorder (IGD). 26.8–83.3% of adolescents meeting criteria for internet addiction have comorbid attention-deficit/hyperactivity disorder. IGD is associated with increased anxiety and social anxiety/phobias. Group counseling, cognitive behavioral therapy, and sports intervention are associated with significant reductions in internet addiction. Summary With the Diagnostic and Statistical Manua...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: ADOLESCENT MEDICINE: Edited by Sara F. Forman and Sarah Pitts Source Type: research
Codependency robs us of a self and self-love. We’ve learned to conceal who we really are because we grew up pleasing, rebelling against, or withdrawing from dysfunctional parents. That sets us up for trauma. As adults, even if we’re successful in some areas, our emotional life isn’t easy. Looking for security and love, most of us struggle to get into or out of relationships. We may remain in unhappy or abusive relationships or try to make painful ones work. Many of us would be content just to find a reprieve from ongoing anxiety or depression. After the Breakup However, ending a relationship isn’t t...
Source: Psych Central - Category: Psychiatry Authors: Tags: Abuse Codependence Domestic Violence PTSD Trauma Violence & Aggression Abusive Relationship Estrangement Guilt no contact Traumatic Experience Source Type: news
Conditions:   Depression;   Anxiety Intervention:   Behavioral: Culturally adapted CBT Sponsor:   Centre for Addiction and Mental Health Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract The cannabinoid receptor 1 (CBR1) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eve...
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research
Publication date: Available online 5 July 2019Source: Pharmacology &TherapeuticsAuthor(s): Marie-Christine Tonon, Hubert Vaudry, Julien Chuquet, Florent Guillebaud, Jinjiang Fan, Olfa Masmoudi-Kouki, David Vaudry, Damien Lanfray, Fabrice Morin, Vincent Prevot, Vassilios Papadopoulos, Jean-Denis Troadec, Jérôme LeprinceAbstractThe existence of specific binding sites for benzodiazepines (BZs) in the brain has prompted the search for endogenous BZ receptor ligands designated by the generic term « endozepines ». This has led to the identification of an 86-amino acid polypeptide capable of displacin...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
Not so long ago, worries about the digital divide represented the anxiety that the rich will have access to more information and more possibilities in every area of life compared to those who cannot afford connected digital devices. Currently, trends show that human connection might become a luxury good for the rich, while poor families might not be able to afford living screen-free in the future. We asked how would that translate into healthcare and what could we do to ensure the treasure of human contact to everyone in the coming decades. Is digital detox becoming a luxury good? Although the techno-dystopian sci-fi...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Bioethics Future of Medicine addiction development divide gap Healthcare human human connection human contact inequality low-income poor rich screen smart smartphone society technology Source Type: blogs
We present an exploratory study of a mobile communication system which intends to improve the mental, physical and social health of a group of vulnerable immigrant women in Spain (n = 71), distinguishing between an intervention group and a non-equivalent control group. We sent automatic text messages (SMS) to the mobile phones of an intervention group formed by immigrant women who used the social services (n = 44). During a 26-day intervention period, the women received 4 daily automatic text messages on their phones, at a predetermined time. We measured mood and depression symptoms at the begin...
Source: Journal of Medical Systems - Category: Information Technology Source Type: research
Conclusions: There are theoretical and practical similarities between exposure to fear cues and cues of addiction, especially regarding extinction learning. However, these processes are also unique, particularly regarding the differing motivational properties of fear versus reward-related stimuli. We propose that unlike exposure for anxiety, CET takes effect by increasing self-control with each unreinforced exposure. We consider reasons for CET's limited use for AUDs, including its lower acceptability to clients and clinicians. We also note the limited evidence for CET for other substance use disorders, highlighting the ne...
Source: Substance Use and Misuse - Category: Addiction Tags: Subst Use Misuse Source Type: research
Authors: Ilario C, Alt A, Bader M, Sentissi O Abstract ADHD is the most common psychiatric disorder of childhood. It is considered to be a neurodevelopmental disorder that may persist from chilhood into adulthood. In childood it is associated with several outcomes such as inattention, hyperactivity and impulsivity. Symptoms may change as a person gets older with an increased risk of developing psychiatric comorbidities such as depression, anxiety and substance addiction. However, recent studies diverge from the traditional perspective. These authors hypothesized that ADHD may appear in adulthood, not as a continuat...
Source: L Encephale - Category: Psychiatry Tags: Encephale Source Type: research
Substance use disorders (SUDs) are a growing public health concern with only a limited number of approved treatments. However, even approved treatments are subject to limited efficacy with high long-term relapse rates. Current treatment approaches are typically a combination of pharmacotherapies and behavioral counselling. Growing evidence and technological advances suggest the potential of brain stimulation techniques for the treatment of SUDs. There are three main brain stimulation techniques that are outlined in this review: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and dee...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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