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Transcranial low-intensity pulsed ultrasound in neurological disorders: mechanisms, therapeutic applications, and translational challenges.

Transcranial low-intensity pulsed ultrasound (LIPUS) is an emerging non-invasive modality with high spatial precision, substantial tissue penetrability, and favorable biosafety. Acting predominantly through mechanical rather than thermal bioeffects, LIPUS modulates mechanosensitive ion channels, intracellular calcium signaling, synaptic transmission, glial activation, neurovascular coupling, and, in selected settings, blood-brain barrier permeability. These features support its growing application in neurological disorders. In this review, we summarize the mechanistic basis of transcranial LIP…

Ultrasound neuromodulation in brain disorders: from mechanotransduction mechanisms to clinical translation.

Brain disorders impose a major global health burden, yet current pharmacological and neuromodulation therapies are often constrained by invasiveness, limited spatial precision, poor access to deep brain structures, or insufficient long-term efficacy. Non-invasive ultrasound neuromodulation has emerged as a promising approach combining high spatial resolution, deep tissue penetration, and reversible modulation. Its biological effects arise from multiscale mechanotransduction involving membrane deformation, mechanosensitive ion channels, intracellular calcium signaling, glial regulation, and neu…

Cardiac Protein Palmitoylation: Mechanisms, Functions, and Therapeutic Potential.

Protein S-palmitoylation is a reversible lipid modification which regulates the localisation, stability, and activity of a substantial fract … view, we focus on the role of S-palmitoylation in cardiac function, highlighting its effects on key ion channels and transporters, including CaV1.2, NaV1.5 and NCX1, and the resulting consequences for cardiac electrophysiology and calcium handling. We also discuss emerging experimental tools and strategies to selectively manipulate S-palmitoylation and their l …

Pathophysiological significance of cholesterol in ciliopathies.

Primary cilia are sensory organelles essential for cellular signaling, the dysfunction of which causes ciliopathies, characterized by polycystic kidney disease, retinopathy, and developmental anomalies. Here, we review recent studies which have shown that cholesterol is a critical mediator of ciliary function and the pathogenesis of ciliopathies. Ciliary membranes show distinct cholesterol enrichment that is essential for the physiological function of various G-protein-coupled receptors and ion channels. Defects in de novo cholesterol synthesis (Smith-Lemli-Opitz syndrome) and peroxisome-facil…

Alteration of Lipid Bilayer Electrical Potential by Phytochemicals and Synthetic Analogs: Implications for Cellular Function.

Phytochemicals, including flavonoids, stilbenoids, alkaloids, terpenoids, and structurally related synthetic small molecules, exhibit a broa … rous cellular processes. Changes in membrane potential impact the function of embedded proteins and ion channels, thereby modulating cell signaling, transport, and pharmacological responses. This review compiles data on how diverse plant and synthetic small molecules alter membrane physical characteristics, particularly the dipole component of the boundary pot …

Hidden Receptor Crosstalk Governs Lymphatic Failure After Cancer Therapy.

Cancer therapy imposes sustained mechanical and biochemical stress on lymphatic tissues, reshaping the signaling environments in which endot … tress, receptor systems that are secondary under homeostatic conditions, including mechanosensitive ion channels, purinergic receptors, and stress-responsive G protein-coupled receptors, can exert disproportionate influence over endothelial transcription, barrier function, contractile coordination, and immune-vascular feedback loops. Sustained activation of th …

Mechanistic insights into flavonoid-mediated regulation of human influenza virus replication.

Influenza A virus (IAV) remains a major global health concern due to its rapid mutation rate, antigenic variability, and the emergence of re … IAV proteins such as hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), and matrix-2 (M2) ion channels. The ability of plant-derived compounds to inhibit viral replication underscores their potential as leads for next-generation influenza therapeutics. Nonetheless, rigorous in vivo studies, mechanistic elucidation, and pharmacokinetic evaluations are …

Magnetothermally responsive fibrin hydrogel for localized neuromodulation.

Magnetic biointerfaces have emerged as powerful tools in neuroscience, enabling significant advances in both neural regeneration and neuromodulation. Magnetothermal neuromodulation using magnetic nanoparticles (MNPs) responsive to alternating magnetic fields (AMFs), offers a remote means of localized thermal stimulation of thermosensitive ion channels, which subsequently modulate neural activity, but clinical translation is limited by poor spatial control and off-target nanoparticle distribution. Here, we introduce a magnetically responsive fibrin hydrogel that spatially confines polyethylene …

The mechanisms and mechanics of aging.

Aging tissues paradoxically stiffen while losing mechanical resilience, becoming fragile, poorly regenerative and chronically inflamed. We r … machinery propagate through focal adhesion signaling, actin-microtubule dynamics, mechanosensitive ion channels and nucleo-cytoskeletal coupling to dysregulate mechanosensitive transcription factors (including YAP/TAZ and MRTF), promote senescence and amplify the senescence-associated secretory phenotype (SASP), which further degrades the ECM. Finally, we hig …

Lipid overload meets S-palmitoylation: a metabolic signalling nexus driving cardiovascular and heart disease.

S-palmitoylation has emerged as a critical integrator of lipid overload and cardiovascular dysfunction. Disordered lipid metabolism inundate … ivotal proteins including the lipid transporter CD36, endothelial nitric oxide synthase (eNOS), key ion channels and the pyroptosis effector gasdermin D (GSDMD). Cycles of palmitate addition and removal regulate membrane residency, foam cell formation, nitric oxide production, calcium handling and inflammatory cell death, thereby linking lipid burden to athero …

Applying Ultrasound to Mechanically and Noninvasively Sensitize Prostate Tumors to TRAIL-Mediated Apoptosis.

Non-surgical and safe prostate cancer (PCa) therapies are in demand. Soluble tumor necrosis factor (TNF-α) related apoptosis inducing ligand (TRAIL), a cancer-specific drug, shows preclinical efficacy but has a short circulation half-life. This research has shown that physiological fluid shear stress activates mechanosensitive ion channels (MSCs), such as Piezo1, enhancing TRAIL-mediated apoptosis in cancer cells. Herein, noninvasive, focal ultrasound (FUS) is implemented to augment the pro-apoptotic effects of TRAIL. Using thermally safe FUS parameters, it is observed that TRAIL sensitivity i…

The p3 peptides (Aβ17-40/42) rapidly form amyloid fibrils that cross-seed with full-length Aβ.

The p3 peptides, Aβ17-40/42, are a common alternative cleavage product of the amyloid precursor protein, and are found in diffuse amyloid deposits of Alzheimer's and Down Syndrome brains. The p3 peptides have been mis-named 'non-amyloidogenic'. Here we show p340/42 peptides rapidly form amyloid fibrils, with kinetics dominated by secondary nucleation. Importantly, cross-seeding experiments, with full-length Aβ induces a strong nucleation between p3 and Aβ peptides. The cross-seeding interaction is highly specific, and occurs only when the C-terminal residues are matched. We have imaged membran

Single-nucleus neuronal transcriptional profiling of male C. elegans uncovers regulators of sex-specific and sex-shared behaviors.

Sexual differentiation of the nervous system drives profound neurobiological and behavioral differences between the sexes across various organisms, including Caenorhabditis elegans. Using single-nucleus RNA sequencing, we profiled and compared adult male and hermaphrodite C. elegans neurons, generating an atlas of adult male-specific and sex-shared neurons. We expanded the molecular map of male-specific neurons and identified highly dimorphic expression of G protein-coupled receptors (GPCRs), neuropeptides, and ion channels. Our data demonstrate sex-shared neurons exhibit substantial heterogen…

Hydrogen Sulfide in Balneology: Physiology, Evidence, and Clinical Translation.

This review integrates the biology and clinical translation of hydrogen sulfide (H2S) in balneology. It frames H2S as a gasotransmitters with dual chemical and biological actions and summarizes the H2S/HS- equilibrium as a function of pH, temperature, and oxygenation, which governs bioaccessibility in sulfurous waters. Endogenous and exogenous sources, transport, and mitochondrial catabolism are outlined, together with core cellular mechanisms: protein persulfidation; activation of Nrf2/ARE; modulation of NF-κB; regulation of ion channels; and engagement of PI3K/Akt, MAPK/ERK, and Wnt pathways…

Snake Venom Three-Finger Neurotoxins and Neurotoxin-Like Proteins: Insights Into Their Structural and Functional Aspects Along With Their Pharmacological Potential.

The three-finger neurotoxins interfere with cholinergic transmission at various postsynaptic sites in the peripheral and central nervous sys … mately 60 years ago, and their discovery has since expanded our knowledge of membrane receptors and ion channels. The interactions of these neurotoxins with receptors are of special interest for their potential use in the treatment of neurodegenerative diseases, pain and cancer. This review focuses on the snake venom neurotoxins and neurotoxin-like proteins an …

Калпайны на перекрестке Спинальной Корды, пластиковость и патология.

Зависящие от кальция протезы цистейна, известные как кальпаины, становятся важными регуляторами физиологии спинного мозга, пластичности и патологии. Прежде всего в мозге они оказывают влияние на широкий спектр процессов в спинном мозге, поддерживая нейронный гомеостаз, формируя как синаптическую, так и имманентную пластичность и видоизменяя глиальные реакции. При дисрегулировании кальпаины способствуют патофизиологии травмирующих и нейродегенеративных расстройств спинного мозга, а также их связанным с ними двигательным и сенсорным осложнениям, включая спастику и нейропатическую боль. Одной из

Совпадение в аннотации оригинала
Calcium-dependent cysteine proteases, known as calpains, emerge as important regulators of spinal cord physiology, plasticity, and pathology … ty and neuropathic pain. A recurring feature of these conditions is calpain-mediated proteolysis of ion channels, transporters, and cytoskeletal proteins, which promotes disinhibition and neuronal hyperexcitability. The resultant protein fragments are examined as prospective biomarkers for damage and disease progression. Meanwhile, promising strategies for neu …

The Formation and Function of the VTA Dopamine System.

The midbrain dopamine system is a sophisticated hub that integrates diverse inputs to control multiple physiological functions, including lo … stood. In this review article, we mainly focus on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, with the hope of obtaining new insight into the formation and function of this vital brain region.

Toxin-derived peptides: An unconventional approach to alleviating cerebral stroke burden and neurobehavioral impairments.

Cerebral stroke is a pressing global health concern, ranking as the second leading cause of mortality and resulting in persistent neurobehav … eptides, with potential in innovative healthcare applications. These venomous components, affecting ion channels, receptors, and transporters, encompass neurochemicals, amino acids, and peptides, making them prime candidates for treating cerebral ischemia and neurological disorders. This review explores the composition, applications, and significance of toxin- …

A Second Drug Binding Site in P2X3.

Purinergic P2X3 receptors form trimeric cation-gated channels, which are activated by extracellular ATP. P2X3 plays a crucial role in chronic cough and affects over 10% of the population. Despite considerable efforts to develop drugs targeting P2X3, the highly conserved structure within the P2X receptor family presents obstacles for achieving selectivity. Camlipixant, a potent and selective P2X3 antagonist, is currently in phase III clinical trials. However, the mechanisms underlying receptor desensitization, ion permeation, principles governing antagonism, and the structure of P2X3 when bound

Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components.

Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, … nom predominantly consists of short proteins acting as neurotoxins (α and β), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptom …