Selenoprotein T, a potential treatment of attention-deficit/hyperactivity disorder and comorbid pain in neonatal 6-OHDA lesioned mice.

pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is well documented in children, adolescents, and adults. According to pathophysiological investigations, the dopaminergic system's dysfunction provides a common basis for ADHD and comorbid pain.

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure.

Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood.

To what extent may aminochrome increase the vulnerability of dopaminergic neurons in the context of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that progresses over time and is characterized by preferential reduction of dopaminergic neurons in the substantia nigra. Although the precise mechanisms leading to cell death in neurodegenerative disorders, such as PD, are not fully understood, it is widely accepted that increased oxidative stress may be a prevalent factor contributing to the deterioration of the nigrostriatal dopaminergic fibers in such conditions. Aminochrome, generated from dopamine (DA) metabolism, plays an important role in multiple pathogenic mechanisms associated with PD.

Emerging roles of ER-resident selenoproteins in brain physiology and physiopathology.

The brain has a very high oxygen consumption rate and is particularly sensitive to oxidative stress. It is also the last organ to suffer from a loss of selenium (Se) in case of deficiency. Se is a crucial trace element present in the form of selenocysteine, the 21st proteinogenic amino acid present in selenoproteins, an essential protein family in the brain that participates in redox signaling.

The SELENOT mimetic PSELT promotes nerve regeneration by increasing axonal myelination in a facial nerve injury model in female rats.

Peripheral nerve injury (PNI) is frequent and many patients suffer lifelong disabilities in severe cases. Although the peripheral nervous system is able to regenerate, its potential is limited. In this study, we tested in a nerve regeneration model in rat the potential beneficial effect of a short mimetic peptide, named PSELT, which derives from SELENOT, an essential thioredoxin-like selenoprotein endowed with neuroprotective and antioxidant activities.

The 26RFa (QRFP)/GPR103 neuropeptidergic system in mice relays insulin signalling into the brain to regulate glucose homeostasis.

Aims/hypothesis: 26RFa (pyroglutamilated RFamide peptide [QRFP]) is a biologically active peptide that regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity at the periphery. 26RFa is also produced by a neuronal population localised in the hypothalamus. In this study we investigated whether 26RFa neurons are involved in the hypothalamic regulation of glucose homeostasis.

Acute but Not Chronic Central Administration of the Neuropeptide 26RFa (QRFP) Improves Glucose Homeostasis in Obese/Diabetic Mice.

Introduction: The aim of the study is to investigate whether acute or chronic central administration of the hypothalamic neuropeptide 26RFa may ameliorate the glycemic control of obese/diabetic mice.

Methods: Mice were treated for 4 months with a high-fat (HF) diet and received a single i.c.

SELENOT Deficiency in the Mouse Brain Impacts Catecholaminergic Neuron Density: An Immunohistochemical, in situ Hybridization and 3D Light-Sheet Imaging Study.

Background: Selenoprotein T (SELENOT), a PACAP-regulated thioredoxin-like protein, plays a role in catecholamine secretion and protects dopaminergic neurons. However, the role of SELENOT in the establishment of the catecholaminergic (CA) neuronal system is not known yet.

Methods: We analyzed by immunohistochemistry and RNAscope in situ hybridization the distribution of SELENOT and the expression of its mRNA, respectively.

Prediction methods for microRNA targets in bilaterian animals: Toward a better understanding by biologists.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Because of their wide network of interactions, miRNAs have become the focus of many studies over the past decade, particularly in animal species. To streamline the number of potential wet lab experiments, the use of miRNA target prediction tools is currently the first step undertaken.

Cell-penetrating, antioxidant SELENOT mimetic protects dopaminergic neurons and ameliorates motor dysfunction in Parkinson's disease animal models.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction for which there is an unmet need for better treatment options. Although oxidative stress is a common feature of neurodegenerative diseases, notably PD, there is currently no efficient therapeutic strategy able to tackle this multi-target pathophysiological process. Based on our previous observations of the potent antioxidant and neuroprotective activity of SELENOT, a vital thioredoxin-like selenoprotein, we designed the small peptide PSELT from its redox active site to evaluate its antioxidant properties in vivo, and its potential polyfunctional activity in PD models.

Tolerant/Persister Cancer Cells and the Path to Resistance to Targeted Therapy.

The capacity of cancer to adapt to treatment and evolve is a major limitation for targeted therapies. While the role of new acquired mutations is well-established, recent findings indicate that resistance can also arise from subpopulations of tolerant/persister cells that survive in the presence of the treatment. Different processes contribute to the emergence of these cells, including pathway rebound through the release of negative feedback loops, transcriptional rewiring mediated by chromatin remodeling and autocrine/paracrine communication among tumor cells and within the tumor microenvironment.

Selenoprotein T: An Essential Oxidoreductase Serving as a Guardian of Endoplasmic Reticulum Homeostasis.

Selenoproteins incorporate the essential nutrient selenium into their polypeptide chain. Seven members of this family reside in the endoplasmic reticulum (ER), the exact function of most of which is poorly understood. Especially, how ER-resident selenoproteins control the ER redox and ionic environment is largely unknown.

Lymphatic and Immune Cell Cross-Talk Regulates Cardiac Recovery After Experimental Myocardial Infarction.

Objective: Lymphatics play an essential pathophysiological role in promoting fluid and immune cell tissue clearance. Conversely, immune cells may influence lymphatic function and remodeling. Recently, cardiac lymphangiogenesis has been proposed as a therapeutic target to prevent heart failure after myocardial infarction (MI).

Chromogranin A preferential interaction with Golgi phosphatidic acid induces membrane deformation and contributes to secretory granule biogenesis.

Chromogranin A (CgA) is a key luminal actor of secretory granule biogenesis at the trans-Golgi network (TGN) level but the molecular mechanisms involved remain obscure. Here, we investigated the possibility that CgA acts synergistically with specific membrane lipids to trigger secretory granule formation. We show that CgA preferentially interacts with the anionic glycerophospholipid phosphatidic acid (PA).

Coronaridine congeners potentiate GABA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner.

To determine whether (+)-catharanthine induces sedative- or anxiolytic/anxiogenic-like activity in male mice, proper animal paradigms were used. The results showed that (+)-catharanthine induces sedative-like activity in the 63-72 mg/Kg dose range in a flumazenil-insensitive manner, but neither this effect nor anxiolytic/anxiogenic-like activity was observed at lower doses. To determine the underlying molecular mechanism of the sedative-like activity, electrophysiological and radioligand binding experiments were performed with (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC] on GABA (GABARs) and glycine receptors (GlyRs).

Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP).

Introduction: 26RFa (pyroglutamyl RFamide peptide (QRFP)) is a biologically active peptide that has been found to control feeding behavior by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism.

Research Design And Methods: 26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro26RFa was replaced by the iCre sequence.

Improving Bioinformatics Prediction of microRNA Targets by Ranks Aggregation.

microRNAs are noncoding RNAs which downregulate a large number of target mRNAs and modulate cell activity. Despite continued progress, bioinformatics prediction of microRNA targets remains a challenge since available software still suffer from a lack of accuracy and sensitivity. Moreover, these tools show fairly inconsistent results from one another.

L-DOPA in Parkinson's Disease: Looking at the "False" Neurotransmitters and Their Meaning.

-3,4-dihydroxyphenylalanine (L-DOPA) has been successfully used in the treatment of Parkinson's disease (PD) for more than 50 years. It fulfilled the criteria to cross the blood-brain barrier and counteract the biochemical defect of dopamine (DA). It remarkably worked after some adjustments in line with the initial hypothesis, leaving a poor place to the plethora of mechanisms involving other neurotransmitters or mechanisms of action beyond newly synthesized DA itself.

Chromogranin A in the early steps of the neurosecretory pathway.

Chromogranin A (CgA) is a soluble glycoprotein stored with hormones and neuropeptides in secretory granules (SG) of most (neuro)endocrine cells and neurons. Since its discovery in 1967, many studies have reported its structural characteristics, biological roles, and mechanisms of action. Indeed, CgA is both a precursor of various biologically active peptides and a granulogenic protein regulating the storage and secretion of hormones and neuropeptides.

The neuropeptide 26RFa in the human gut and pancreas: potential involvement in glucose homeostasis.

Objective: Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients.