Neuronal ion channel modulation by Drimys winteri compounds: Opening a new chemical space to neuropharmacology.

Numerous pathological states of the nervous system involve alterations in neuronal excitability and synaptic dysfunction, which depend on the function of ion channels. Due to their critical involvement in health and disease, the search for new compounds that modulate these proteins is still relevant. Traditional medicine has long been a rich source of neuroactive compounds.

The Alkaloid Gelsemine Reduces Aβ Peptide Toxicity by Targeting Transglutaminase Type 2 Enzyme.

Gelsemine, a naturally occurring indole alkaloid derived from plants of the species of the Gelsemiaceae family, has been extensively investigated for its neuroprotective and anti-inflammatory properties. Recent studies have demonstrated that gelsemine exerts neuroprotective effects against beta-amyloid (Aβ) oligomers, a key neurotoxic peptide implicated in the pathogenesis of Alzheimer's disease (AD). However, despite these beneficial effects, the precise molecular targets underlying gelsemine's neuroprotective actions in AD remain unidentified.

Phase IIa randomized placebocontrolled clinical trial to evaluate the efficacy of bromhexine in combination with standard therapy in the early treatment of COVID-19 in primary care patients.

Unlabelled: The continuous appearance of SARS-CoV-2 variants with both increased transmission and immune evading potential, in addition to the reluctance of some populations to be vaccinated, supports the search for alternative treatments to protect against the viral infection consequences. Bromhexine is a well-known, over-the counter, expectorant which have garnered interest for the potential prevention and treatment of COVID-19.

Aim: To evaluate the efficacy of oral bromhexine in patients with mild to moderate symptomatic active SARS-CoV-2 infection.

Deciphering the Neurotoxic Effects of .

is a globally recognized dinoflagellate associated with harmful algal blooms and massive fish kills along southern Chilean coasts. Its toxicity varies with environmental factors and genetic diversity. While is traditionally linked to neurotoxins like gymnodimines (GYMs), analysis of the strain CREAN-KS02 from Chile's Aysén Region (43° S) revealed no presence of toxins associated with this genus, such as gymnodimines, brevetoxins, or brevenal.

Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.

Ionotropic glycine receptors (GlyRs) are chloride-permeable ligand-gated ion channels expressed in the nervous system. Alterations to glycinergic inhibition and the generation of dysfunctional GlyRs have been linked to chronic pain, a widely prevalent disease. Positive allosteric modulators (PAMs) targeting GlyRs exerted analgesic effects, motivating research on glycinergic PAMs as potential pain therapies.

Molecular Pharmacology of Alkaloids on Inhibitory Receptors.

Indole alkaloids are the main bioactive molecules of the genus plants. Diverse reports have shown the beneficial actions of alkaloids on the pathological states of the central nervous system (CNS). Nevertheless, alkaloids are toxic for mammals.

Elephant Black Garlic's Beneficial Properties for Hippocampal Neuronal Network, Chemical Characterization and Biological Evaluation.

Garlic has been used for decades as an important food and additionally for its beneficial properties in terms of nutrition and ancestral therapeutics. In this work, we compare the properties of fresh (WG) and aged (BG) extract obtained from elephant garlic, harvested on Chiloe Island, Chile. BG was prepared from WG with a 20-day aging process under controlled temperature and humidity conditions.

New Benzodihydrofuran Derivatives Alter the Amyloid β Peptide Aggregation: Strategies To Develop New Anti-Alzheimer Drugs.

Alzheimer's disease is a neurodegenerative disorder that is the leading cause of dementia in elderly patients. Amyloid-β peptide (1-42 oligomers) has been identified as a neurotoxic factor, triggering many neuropathologic events. In this study, 15 chalcones were synthesized employing the Claisen-Schmidt condensation reaction, starting from a compound derived from fomannoxine, a natural benzodihydrofuran whose neuroprotective activity has been proven and reported, and methyl aromatic ketones with diverse patterns of halogenated substitution.

Partial Inhibition of Complex I Restores Mitochondrial Morphology and Mitochondria-ER Communication in Hippocampus of APP/PS1 Mice.

Alzheimer's disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with the small molecule CP2 induces an adaptive stress response, activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, Aβ and pTau accumulation, improved synaptic and mitochondrial functions, and blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model of AD.

TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer's disease.

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD's main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca-dependent proteins transamidation, including the Aβ peptide.

Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation.

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD; regulating processes such as cell migration and synaptic transmission.

Modulation of GABA receptors and of GABAergic synapses by the natural alkaloid gelsemine.

The plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the plants, have replicated these therapeutic and toxic actions in experimental behavioral models.

Neuroprotective Properties of Eudesmin on a Cellular Model of Amyloid-β Peptide Toxicity.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. One of the hallmarks in AD is amyloid-β peptide (Aβ) accumulation, where the soluble oligomers of Aβ (AβOs) are the most toxic species, deteriorating the synaptic function, membrane integrity, and neuronal structures, which ultimately lead to apoptosis. Currently, there are no drugs to arrest AD progression, and current scientific efforts are focused on searching for novel leads to control this disease.

Antiseizure medication in early nervous system development. Ion channels and synaptic proteins as principal targets.

The main strategy for the treatment of epilepsy is the use of pharmacological agents known as antiseizure medication (ASM). These drugs control the seizure onset and improves the life expectancy and quality of life of patients. Several ASMs are contraindicated during pregnancy, due to a potential teratogen risk.

Metabolic profile and antioxidant capacity of five Berberis leaves species: A comprehensive study to determine their potential as natural food or ingredient.

A comprehensive study of bioactive compounds was carried out in the leaves of the main Berberis species growing in Chile (Berberis microphylla, Berberis darwinii, Berberis empetrifolia, Berberis trigona, and the introduced Berberis vulgaris). We identified 117 compounds, by a detailed analysis of each molecule, including phenolic acids, alkaloids, flavonols, and other compounds, using high-performance liquid chromatography and high-resolution mass spectrometry. Quantitative analysis of main compound was also included for all species.

Microglial Activation Modulated by P2X4R in Ischemia and Repercussions in Alzheimer's Disease.

There are over 80 million people currently living who have had a stroke. The ischemic injury in the brain starts a cascade of events that lead to neuronal death, inducing neurodegeneration which could lead to Alzheimer's disease (AD). Cerebrovascular diseases have been suggested to contribute to AD neuropathological changes, including brain atrophy and accumulation of abnormal proteins such as amyloid beta (Aβ).

PrP as a Transducer of Physiological and Pathological Signals.

After the discovery of prion phenomenon, the physiological role of the cellular prion protein (PrP ) remained elusive. In the past decades, molecular and cellular analysis has shed some light regarding interactions and functions of PrP in health and disease. PrP , which is located mainly at the plasma membrane of neuronal cells attached by a glycosylphosphatidylinositol (GPI) anchor, can act as a receptor or transducer from external signaling.

Phenolic Compounds in Calafate Berries Encapsulated by Spray Drying: Neuroprotection Potential into the Ingredient.

Calafate is a berry rich in anthocyanins that presents higher content of polyphenols than other fruits. Its compounds have been described previously, however, the potential thereof in preventing and treating degenerative disorders has not yet been studied. Due to its astringency, the consumption of this berry in its natural state is limited.

Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer's disease.

Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer's Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients.

Deciphering the role of PGC-1α in neurological disorders: from mitochondrial dysfunction to synaptic failure.

The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis.

The Administration of the Synbiotic 6c3 Strain, Inulin and Fructooligosaccharide Decreases the Concentrations of Indoxyl Sulfate and Kidney Damage in a Rat Model.

Indoxyl sulfate (IS) is involved in the progression of chronic kidney disease (CKD) and in its cardiovascular complications. One of the approaches proposed to decrease IS is the administration of synbiotics. This work aimed to search for a probiotic strain capable to decrease serum IS levels and mix it with two prebiotics (inulin and fructooligosaccharide (FOS)) to produce a putative synbiotic and test it in a rat CKD model.

Stereospecific Inhibition of Ethanol Potentiation on Glycine Receptor by M554 Stereoisomers.

Blocking the interaction between the Gβγ protein and the glycine receptor (GlyR) has emerged as a promising pharmacological strategy to treat acute alcohol intoxication by inhibiting ethanol potentiation on GlyR. M554 is a recently discovered small molecule capable of binding to Gβγ with potent and inhibitory activity. This compound has been tested as a mixture of diastereomers, and no information is available concerning the stereospecific activity of each species, which is critical to pursue efforts on lead optimization and drug development.

Inhibition of the Glycine Receptor alpha 3 Function by Colchicine.

Colchicine is a plant alkaloid that is widely used as a therapeutic agent. It is widely accepted that colchicine reduces the production of inflammatory mediators mainly by altering cytoskeleton dynamics due to its microtubule polymerization inhibitory activity. However, other lines of evidence have shown that colchicine exerts direct actions on the function of ion channels, which are independent of cytoskeleton alterations.

Altered Glutaminase 1 Activity During Neurulation and Its Potential Implications in Neural Tube Defects.

The neurulation process is regulated by a large amount of genetic and environmental factors that determine the establishment, folding, and fusion of the neural plate to form the neural tube, which develops into the main structure of the central nervous system. A recently described factor involved in this process is glutamate. Through NMDA ionotropic receptor, glutamate modifies intracellular Ca dynamics allowing the oriented cell migration and proliferation, essentials processes in neurulation.