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Calcium channel blockers and Alzheimer's disease.

Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofibrillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers involved in Alzheimer's disease therapy.

Инфекция аденовируса 4 серотипа подталкивает уровни кальция к эндоплазмическому ретикулумному стрессу, чтобы стимулировать вирусное воспроизведение в клетках LMH.

Синдром гепатита-гидроперикардия (HHS), вызываемый серотипом 4 птицы (FAdV-4), является острым и крайне смертельным заболеванием, представляющим серьезную угрозу для мировой птицеводческой промышленности. Ионы кальция служат важными вторыми посыльными, которые регулируют несколько этапов вирусного жизненного цикла, включая вход, воспроизведение и сборку. Однако вопрос о том, использует ли FADV-4 внутриклеточный сигнал кальция для облегчения его собственного воспроизведения, остается в значительной степени неисследованным. Здесь мы показываем, что инфекция FADV-4 значительно повышает уровень вн

Совпадение в аннотации оригинала
Hepatitis-hydropericardium syndrome (HHS), caused by fowl adenovirus serotype 4 (FAdV-4), is an acute and highly fatal disease that poses a … e cycle, including entry, replication, and assembly. However, whether FAdV-4 exploits intracellular calcium signaling to facilitate its own replication remains largely unexplored. Here, we demonstrate that FAdV-4 infection significantly elevates intracellular calcium levels in LMH cells in a time- and dose-dependent manner. Mechanistically, FAdV-4 induces endoplasm …

Defining the interactome of the pancreas-specific SPCA2 isoform (SPCA2C) identifies unique links to store-operated Ca2+ entry.

Calcium (Ca2+) is critical for normal cell function, and several protein networks are required for Ca2+ signaling. In the pancreas, regulated changes in cytosolic Ca2+ allow for the exocytosis of zymogen granules, and altered Ca2+ signaling underlies pancreatic pathologies. Previously, our laboratory showed a pancreas-specific isoform of secretory pathway Ca2+-ATPase 2 (also known as calcium-transporting ATPase type 2C member 2; SPCA2), termed SPCA2C (gene name Atp2c2c, C-terminally truncated form), affects multiple pathways involved in Ca2+ homeostasis. The goal of this study was to define th

Cholic acid activation of GPBAR1 does not induce or exacerbate acute pancreatitis but promotes exocrine pancreatic secretion.

Obstruction of bile ducts due to gallstones can lead to biliary acute pancreatitis (BAP). According to Perides et al., G protein-coupled bil … ro to observe the effect of CA-induced cAMP signaling on CCK-induced physiological and pathological calcium signaling. In vivo evaluations involved reverse biliopancreatic duct injections of 5 % sodium taurocholate (STC) or 5 % CA in rats. CA induced intracellular cAMP signaling in a concentration-dependent manner without increasing the intracellular Ca2+ concentra …

Delineation of altered brain proteins associated with furious rabies virus infection in dogs by quantitative proteomics.

Rabies is a fatal zoonotic disease caused by rabies virus (RABV). Despite the existence of control measures, dog-transmitted human rabies ac … ated proteins were statistically significant in infected samples. GO annotation and IPA showed that calcium signaling and calcium transport, efficient neuronal function, metabolic pathway associated proteins were mostly altered during this infection. Total 34 proteins including 10 down-regulated proteins pertaining to calcium signaling and calcium transport pathway …

Ca2+/calmodulin-driven functions mediated by extracellular vesicles: a physiopathological perspective.

Extracellular vesicles (EVs), including exosomes and microvesicles, secreted by a wide range of eukaryotic cells, are now well-established mediators of intercellular communication, acting through their uptake by recipient cells at local or distant sites. This occurs after delivering their cargo, a variety of RNAs, lipids, and proteins, which regulate many cellular functions in health and disease states. Among the exosomal cargos, the Ca2+-sensor protein calmodulin (CaM), as well as several Ca2+/CaM-regulated proteins, are frequently found in EVs, potentially playing important roles in the func

On the G protein-coupling selectivity of the native A2B adenosine receptor.

A2B adenosine receptor (A2BAR) activation induces Gs-dependent cyclic AMP accumulation. However, A2BAR G protein-coupling to other signaling events, e.g. ERK1/2 and calcium, is not well documented. We explored Gi, Gq/11 and Gs coupling in 1321 N1 astrocytoma, HEK293, and T24 bladder cancer cells endogenously expressing human A2BAR, using NECA or nonnucleoside BAY60-6583 as agonist, selective Gi, Gs and Gq/11 blockers, and CRISPR/Cas9-based Gq- and Gs-null HEK293 cells. In HEK293 cells, A2BAR-mediated ERK1/2 activity occurred via both Gi and Gs, but not Gq/11. However, HEK293 cell calcium mobil

Nitric oxide cross-talks during low-temperature stress in plants.

Nitric oxide (NO) is a crucial signaling molecule, playing a pivotal role in response to low-temperature (LT) stress in plants. NO mediates cold acclimation mainly via modulation of redox homeostasis, phytohormone signaling, calcium signaling, transcription factors, and other secondary messengers. This review explores the intricate dialogue between NO and various plant growth regulators. NO cross-talk with phytohormones like ethylene, abscisic acid, brassinosteroids, melatonin and salicylic acid, mitigates chilling injuries and alleviates physiological damage during LT. Secondary metabolites s…

Registration of Calcium Transients in Mouse Neuromuscular Junction with High Temporal Resolution using Confocal Microscopy.

Estimation of the presynaptic calcium level is a key task in studying synaptic transmission since calcium entry into the presynaptic cell triggers a cascade of events leading to neurotransmitter release. Moreover, changes in presynaptic calcium levels mediate the activity of many intracellular proteins and play an important role in synaptic plasticity. Studying calcium signaling is also important for finding ways to treat neurodegenerative diseases. The neuromuscular junction is a suitable model for studying synaptic plasticity, as it has only one type of neurotransmitter. This article describ…

Bibliometric analysis of calcium channel research (2010-2019).

Calcium channels are involved in pathologies across all the major therapeutic areas involving the cardiac, neurological, metabolic, and respiratory systems. Although calcium channels have been the hotspot of multidisciplinary research for decades, the hotspots and frontier trends of calcium channel research have not been comprehensively analyzed by bibliometrics. Here, we collected scientific publications on calcium channel research in the past decade to explore the hotspots and frontier directions of calcium channel research by bibliometric analysis. Publications were retrieved from the Web o

Multi-omic analysis revealed the therapeutic mechanisms of Alpinia oxyphylla fructus water extract against bladder overactivity in spontaneously hypertensive rats.

OBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to allevi … re. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFβ1, p-SMAD3, collagen III, Gq and PLCβ1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predi …

Ca2+ influx into lily pollen grains through a hyperpolarization-activated Ca2+-permeable channel which can be regulated by extracellular CaM.

Confocal laser scanning microscopy (CLSM) and whole-cell patch-clamp were used to investigate the role of Ca2+ influx in maintaining the cytosolic Ca2+ concentration ([Ca2+]c) and the features of the Ca2+ influx pathway in germinating pollen grains of Lilium davidii D. [Ca2+]c decreased when Ca2+ influx was inhibited by EGTA or Ca2+ channel blockers. A hyperpolarization-activated Ca2+-permeable channel, which can be suppressed by trivalent cations, verapamil, nifedipine or diltiazem, was identified on the plasma membrane of pollen protoplasts with whole-cell patch-clamp recording. Calmodulin (

Mg2+ in β-TCP/Mg-Zn composite enhances the differentiation of human bone marrow stromal cells into osteoblasts through MAPK-regulated Runx2/Osx.

Inducing the osteogenic differentiation from bone marrow stromal cells (BMSCs) might be a potent strategy for treating bone loss and nonunion during fracture and improving fracture healing. Among several signaling pathways involved, mitogen-activated protein kinases (MAPKs) have been reported to play a critical role. Magnesium (Mg)-based alloys, including Mg-Zn alloy, have been used clinically as implants in the musculoskeletal field and could promote BMSC osteogenic differentiation. However, the underlying mechanisms remain unclear. In this study, we produced Mg-Zn alloy consists of Mg and lo

HIV-1-associated inflammation and antiretroviral therapy regulate astrocyte endoplasmic reticulum stress responses.

Antiretroviral (ARV) therapy (ART) has effectively suppressed the incidence of human immunodeficiency virus (HIV)-associated dementia in HIV … interaction with the calcium-binding chaperone, calnexin. IL-1β and abacavir enhanced intracellular calcium signaling in astrocytes in the absence of extracellular calcium, illustrating ER-associated calcium release. Alternatively, calcium evoked in response to HAND-relevant stimuli led to mitochondrial permeability transition pore (mPTP) opening in human astrocyte …

Unravelıng non-canonıcal Wnt sıgnalıng ın neural development and dısorders: a revıew of Wnt/PCP and Wnt/ca²⁺ pathways.

Non-canonical Wnt signaling pathways, particularly the Planar Cell Polarity (Wnt/PCP) and Wnt/Ca²⁺ branches, play critical roles in regulating neural development and maintaining cellular homeostasis within the nervous system. This review provides a comprehensive evaluation of the molecular and cellular functions of these pathways, with a focus on their involvement in cytoskeletal dynamics, cellular polarity, and calcium signaling. Non-canonical Wnt signaling is essential for key neurodevelopmental processes, including neural tube closure, neuronal migration, axon guidance, and synaptic plastic…

Defining the potential role of the mineralocorticoid receptor in musculoskeletal health and bone crosstalk with other tissues.

Excessive mineralocorticoid receptor (MR) activation in the heart and vasculature leads to pathological effects such as extracellular matrix accumulation, oxidative stress, and sustained inflammation. While MR's role in cardiovascular and renal systems is well understood, MR signaling has also been implicated as a key driver of homeostasis and pathological changes in several other body systems, including skeletal muscle and adipose tissue. The glucocorticoid receptor (GR) and MR are structurally and functionally linked, sharing 95% similarity in DNA-binding domains and recognizing many of the

Protein S-sulfhydration: Unraveling the prospective of hydrogen sulfide in the brain, vasculature and neurological manifestations.

Hydrogen sulfide (H2S) and hydrogen polysulfides (H2Sn) are essential regulatory signaling molecules generated by the entire body, including the central nervous system. Researchers have focused on the classical H2S signaling from the past several decades, whereas the last decade has shown the emergence of H2S-induced protein S-sulfhydration signaling as a potential therapeutic approach. Cysteine S-persulfidation is a critical paradigm of post-translational modification in the process of H2S signaling. Additionally, studies have shown the cross-relationship between S-sulfhydration and other cys

Adapting techniques for calcium imaging in muscles of adult Brugia malayi.

Brugia malayi is a human filarial nematode parasite that causes lymphatic filariasis or 'elephantiasis' a disfiguring neglected tropical disease. This parasite is a more tractable nematode parasite for the experimental study of anthelmintic drugs and has been studied with patch-clamp and RNAi techniques. Unlike in C. elegans however, calcium signaling in B. malayi or other nematode parasites has not been achieved, limiting the studies of the mode of action of anthelmintic drugs. We describe here the development of calcium imaging methods that allow us to characterize changes in cellular calciu…

Activation of the EGFR/p38/JNK pathway by mitochondrial-derived hydrogen peroxide contributes to oxygen-induced contraction of ductus arteriosus.

UNLABELLED: Oxygen-induced contraction of the ductus arteriosus (DA) involves a mitochondrial oxygen sensor, which signals pO2 in the DA smooth muscle cell (DASMC) by increasing production of diffusible hydrogen peroxide (H2O2). H2O2 stimulates vasoconstriction by regulating ion channels and Rho kinase, leading to calcium influx and calcium sensitization. Because epidermal growth factor receptor (EGFR) signaling is also redox regulated and participates in oxygen sensing and vasoconstriction in other systems, we explored the role of the EGFR and its signaling cascade (p38 and c-Jun N-amino-term

Therapeutic implications of novel peptides targeting ER-mitochondria Ca2+-flux systems.

Intracellular Ca2+-flux systems located at the ER-mitochondrial axis govern mitochondrial Ca2+ balance and cell fate. Multiple yet incurable pathologies are characterized by insufficient or excessive Ca2+ fluxes toward the mitochondria, in turn leading to aberrant cell life or death dynamics. The discovery and ongoing molecular characterization of the main interorganellar Ca2+ gateways have resulted in a novel class of peptide tools able to regulate relevant protein-protein interactions (PPIs) underlying this signaling scenario. Here, we review peptides, molecularly derived from Ca2+-flux syst