Unveiling the agonistic properties of Preyssler-type Polyoxotungstates on purinergic P2 receptors.

The Preyssler-type polyoxotungstate ({PW}) belongs to the family of polyanionic metal-oxides formed by group V and VI metal ions, such as V, Mo and W, commonly known as polyoxometalates (POMs). POMs have demonstrated inhibitory effect on a significant number of ATP-binding proteins in vitro. Purinergic P2 receptors, widely expressed in eukaryotic cells, contain extracellularly oriented ATP-binding sites and play many biological roles with health implications.

Store-Operated Calcium Entry Inhibition and Plasma Membrane Calcium Pump Upregulation Contribute to the Maintenance of Resting Cytosolic Calcium Concentration in A1-like Astrocytes.

Highly neurotoxic A1-reactive astrocytes have been associated with several human neurodegenerative diseases. Complement protein C3 expression is strongly upregulated in A1 astrocytes, and this protein has been shown to be a specific biomarker of these astrocytes. Several cytokines released in neurodegenerative diseases have been shown to upregulate the production of amyloid β protein precursor (APP) and neurotoxic amyloid β (Aβ) peptides in reactive astrocytes.

Internalized Amyloid-β (1-42) Peptide Inhibits the Store-Operated Calcium Entry in HT-22 Cells.

Dysregulation in calcium signaling pathways plays a major role in the initiation of Alzheimer's disease (AD) pathogenesis. Accumulative experimental evidence obtained with cellular and animal models, as well as with AD brain samples, points out the high cytotoxicity of soluble small oligomeric forms of amyloid-β peptides (Aβ) in AD. In recent works, we have proposed that Aβ-calmodulin (CaM) complexation may play a major role in neuronal Ca signaling, mediated by CaM-binding proteins (CaMBPs).

Inhibition of SERCA and PMCA Ca-ATPase activities by polyoxotungstates.

Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phosphotungstate anions [PWO] (intact, {PW}), [PWO] (monolacunary, {PW}), [PWO] (trilacunary, {PW}), [HPWO] (hexalacunary, {PW}), [HPWVO] (trivanadium-substituted, {PWV}) and by Preyssler-type anion [NaPWO] ({PW}). The speciation in the solutions of tested POTs was investigated by P and V NMR spectroscopy.

Special Issue "Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration".

Tissue degeneration is an event shared by many, if not all, age-related pathologies [...

The Plasma Membrane Ca-ATPase, a Molecular Target for Tau-induced Cytosolic Calcium Dysregulation.

Disruption of calcium (Ca) homeostasis is emerging as a prevalent feature of aging and aging-associated neurodegenerative diseases, including Alzheimer's disease (AD), the most common type of tauopathy. This disease is characterized by the combined presence of extracellular neuritic plaques composed by amyloid β-peptides (Aβ) and neurofibrillary tangles of tau. The association of calcium dyshomeostasis with Aβ has been extensively studied, however its link with tau has been less investigated.

Design and Experimental Evaluation of a Peptide Antagonist against Amyloid β(1-42) Interactions with Calmodulin and Calbindin-D28k.

Amyloid β (Aβ(1-42)) oligomers have been linked to the pathogenesis of Alzheimer's disease (AD). Intracellular calcium (Ca) homeostasis dysregulation with subsequent alterations of neuronal excitability has been proposed to mediate Aβ neurotoxicity in AD. The Ca binding proteins calmodulin (CaM) and calbindin-D28k, whose expression levels are lowered in human AD brains, have relevant roles in neuronal survival and activity.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.

Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer's Disease on the Pump Activity.

Since dysregulation of intracellular calcium (Ca) levels is a common occurrence in neurodegenerative diseases, including Alzheimer's disease (AD), the study of proteins that can correct neuronal Ca dysregulation is of great interest. In previous work, we have shown that plasma membrane Ca-ATPase (PMCA), a high-affinity Ca pump, is functionally impaired in AD and is inhibited by amyloid-β peptide (Aβ) and tau, two key components of pathological AD hallmarks. On the other hand, sorcin is a Ca-binding protein highly expressed in the brain, although its mechanism of action is far from being clear.

The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer's Disease.

Intraneuronal amyloid β (Aβ) oligomer accumulation precedes the appearance of amyloid plaques or neurofibrillary tangles and is neurotoxic. In Alzheimer's disease (AD)-affected brains, intraneuronal Aβ oligomers can derive from Aβ peptide production within the neuron and, also, from vicinal neurons or reactive glial cells. Calcium homeostasis dysregulation and neuronal excitability alterations are widely accepted to play a key role in Aβ neurotoxicity in AD.

Binding of Amyloid β(1-42)-Calmodulin Complexes to Plasma Membrane Lipid Rafts in Cerebellar Granule Neurons Alters Resting Cytosolic Calcium Homeostasis.

Lipid rafts are a primary target in studies of amyloid β (Aβ) cytotoxicity in neurons. Exogenous Aβ peptides bind to lipid rafts, which in turn play a key role in Aβ uptake, leading to the formation of neurotoxic intracellular Aβ aggregates. On the other hand, dysregulation of intracellular calcium homeostasis in neurons has been observed in Alzheimer's disease (AD).

The endoplasmic reticulum Ca -ATPase SERCA2b is upregulated in activated microglia and its inhibition causes opposite effects on migration and phagocytosis.

Activation of microglia is an early immune response to damage in the brain. Although a key role for Ca as trigger of microglial activation has been considered, little is known about the molecular scenario for regulating Ca homeostasis in these cells. Taking into account the importance of the endoplasmic reticulum as a cellular Ca store, the sarco(endo)plasmic reticulum Ca -ATPase (SERCA2b) is an interesting target to modulate intracellular Ca dynamics.

Methylene Blue Blocks and Reverses the Inhibitory Effect of Tau on PMCA Function.

Methylene blue (MB) is a synthetic phenothiazine dye that, in the last years, has generated much debate about whether it could be a useful therapeutic drug for tau-related pathologies, such as Alzheimer's disease (AD). However, the molecular mechanism of action is far from clear. Recently we reported that MB activates the plasma membrane Ca-ATPase (PMCA) in membranes from human and pig tissues and from cells cultures, and that it could protect against inactivation of PMCA by amyloid β-peptide (Aβ).

Correction to: STIM1 deficiency is linked to Alzheimer's disease and triggers cell death in SH-SY5Y cells by upregulation of L-type voltage-operated Ca entry.

The original publication of this paper contains errors.

STIM1 deficiency is linked to Alzheimer's disease and triggers cell death in SH-SY5Y cells by upregulation of L-type voltage-operated Ca entry.

Unlabelled: STIM1 is an endoplasmic reticulum protein with a role in Ca mobilization and signaling. As a sensor of intraluminal Ca levels, STIM1 modulates plasma membrane Ca channels to regulate Ca entry. In neuroblastoma SH-SY5Y cells and in familial Alzheimer's disease patient skin fibroblasts, STIM1 is cleaved at the transmembrane domain by the presenilin-1-associated γ-secretase, leading to dysregulation of Ca homeostasis.

Methylene blue activates the PMCA activity and cross-interacts with amyloid β-peptide, blocking Aβ-mediated PMCA inhibition.

The phenothiazine methylene blue (MB) is attracting increasing attention because it seems to have beneficial effects in the pathogenesis of Alzheimer's disease (AD). Among other factors, the presence of neuritic plaques of amyloid-β peptide (Aβ) aggregates, neurofibrilar tangles of tau and perturbation of cytosolic Ca are important players of the disease. It has been proposed that MB decreases the formation of neuritic plaques due to Aβ aggregation.

Functional interplay between plasma membrane Ca-ATPase, amyloid β-peptide and tau.

It is well known that dysregulation of Ca homeostasis is involved in Alzheimeŕs disease (AD), a neurodegenerative disorder characterized by the presence of toxic aggregates of amyloid β-peptide (Aβ) and neurofibrillary tangles of tau. Alteration of calcium signaling has been linked to Aβ and tau pathologies, although the understanding of underlying molecular and cellular mechanisms is far from clear. This review summarizes the functional inhibition of plasma membrane Ca-ATPase (PMCA) by Aβ and tau, and its modulation by calmodulin and the ionic nature of phospholipids.

High affinity binding of amyloid β-peptide to calmodulin: Structural and functional implications.

Amyloid β-peptides (Aβ) are a major hallmark of Alzheimer's disease (AD) and their neurotoxicity develop with cytosolic calcium dysregulation. On the other hand, calmodulin (CaM), a protein which plays a major multifunctional role in neuronal calcium signaling, has been shown to be involved in the regulation of non-amyloidogenic processing of amyloid β precursor protein (APP). Using fluorescent 6-bromoacetyl-2-dimethylaminonaphthalene derivatives of CaM, Badan-CaM, and human amyloid β(1-42) HiLyte™-Fluor555, we show in this work that Aβ binds with high affinity to CaM through the neurotoxic Aβ25-35 domain.

Evaluation of toxic, cytotoxic and genotoxic effects of phytol and its nanoemulsion.

Phytol (PYT) is a diterpenoid having important biological activity. However, it is a water non-soluble compound. This study aims to prepare PYT nanoemulsion (PNE) and evaluation of toxic, cytotoxic and genotoxic activities of PYT and PNE.

Current aspects of polycystic ovary syndrome: A literature review.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with variable prevalence, affecting about one in every 15 women worldwide. The diagnosis of polycystic ovary syndrome requires at least two of the following criteria: oligoovulation and/or anovulation, clinical and/or biochemical evidence of hyperandrogenism and morphology of polycystic ovaries. Women with PCOS appear to have a higher risk of developing metabolic disorders, hypertension and cardiovascular disorders.

Ascorbic acid in the prevention and treatment of cancer.

This review is aimed at the systematic mapping of ascorbic acid in the prevention and/or treatment of cancer in clinical and non-clinical studies from 2011 to 2015, in order to understand dose-response variations as well as its mechanisms of action as an antioxidant and antitumor agent. Seventy-eight articles were retrieved from the PubMed/Bireme database, of which only 30 included ascorbic acid in the prevention and/or treatment of cancer. However, there are controversies regarding doses and a lack of clinical studies featuring its mechanism of action more clearly.

Phospholipids and calmodulin modulate the inhibition of PMCA activity by tau.

The disruption of Ca signaling in neurons, together with a failure to keep optimal intracellular Ca concentrations, have been proposed as significant factors for neuronal dysfunction in the Ca hypothesis of Alzheimer's disease (AD). Tau is a protein that plays an essential role in axonal transport and can form abnormal structures such as neurofibrillary tangles that constitute one of the hallmarks of AD. We have recently shown that plasma membrane Ca-ATPase (PMCA), a key enzyme in the maintenance of optimal cytosolic Ca levels in cells, is inhibited by tau in membrane vesicles.

Therapeutic Potential of Essential Oils Focusing on Diterpenes.

Among all plant derivates, essential oils (EOs) have gained the attention of many scientists. Diterpenes, a family of components present in some EO, are becoming a milestone in the EOs world. The goal of this review is to describe a scenario of diterpenes taking into health-consumption deportment.

Fahr's Syndrome and Secondary Hypoparathyroidism.

A typical case of Fahr's syndrome is described in a 76-year-old Brazilian female who underwent a total thyroidectomy three decades ago. Six years before the current admission, she started with generalized tonic-clonic seizures. Associated disorders involved extra-pyramidal, cognitive, nocturnal terror and mood changes.

An improved method for expression and purification of functional human Ca(2+) transporter PMCA4b in Saccharomyces cerevisiae.

Human plasma membrane calcium ATPases (PMCAs) are highly regulated transporters responsible for the extrusion of calcium out of the cell. Since calcium homeostasis is implicated in several diseases and neurodegenerative disorders, understanding PMCAs activity is crucial. One of the major hindrances is the availability of these proteins for functional and structural analysis.