Endothelial Dysfunction in Neurodegenerative Diseases

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2909 - 2909

Опубликована: Фев. 2, 2023

The cerebral vascular system stringently regulates blood flow (CBF). components of the blood–brain barrier (BBB) protect brain from pathogenic infections and harmful substances, efflux waste, exchange substances; however, diseases develop in cases vessel injuries BBB dysregulation. Vascular pathology is concurrent with mechanisms underlying aging, Alzheimer’s disease (AD), dementia (VaD), which suggests its involvement these mechanisms. Therefore, present study, we reviewed role dysfunction aging neurodegenerative diseases, particularly AD VaD. During development aforementioned changes occur morphology local cells, which, turn, alter CBF, fluid dynamics, integrity. Chronic inflammation dysregulation further exacerbate dysfunction. Multitudinous processes affect cerebrovascular system, whose causes cognitive impairment. Knowledge regarding pathophysiology molecular may lead to discovery clinically relevant biomarkers, facilitate imaging for prevention treatment.

Язык: Английский

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Choroid Plexus Aquaporins in CSF Homeostasis and the Glymphatic System: Their Relevance for Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(1), С. 878 - 878

Опубликована: Янв. 3, 2023

The glymphatic system, a fluid-clearance pathway involved in brain waste clearance, is known to be impaired neurological disorders, including Alzheimer’s disease (AD). For this reason, it important understand the specific mechanisms and factors controlling function. This enables flow of cerebrospinal fluid (CSF) into subsequently interstitium, supported by aquaporins (AQPs). Continuous CSF transport through parenchyma critical for effective drainage solutes, such as toxic proteins, system. However, balance between production secretion from choroid plexus, AQP regulation, also needed. Thus, any condition that affects homeostasis will interfere with removal clearance subsequent processes neurodegeneration. In review, we highlight role AQPs plexus modulation and, consequently, pathway, special focus on AD.

Язык: Английский

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Protective roles of peroxiporins AQP0 and AQP11 in human astrocyte and neuronal cell lines in response to oxidative and inflammatory stressors

Bioscience Reports, Год журнала: 2024, Номер 44(3)

Опубликована: Март 1, 2024

Abstract In addition to aquaporin (AQP) classes AQP1, AQP4 and AQP9 known be expressed in mammalian brain, our recent transcriptomic analyses identified AQP0 AQP11 human cortex hippocampus at levels correlated with age Alzheimer’s disease (AD) status; however, protein localization remained unknown. Roles of transporting hydrogen peroxide (H2O2) lens kidney prompted hypothesis that up-regulation brain might similarly protective. Established cell lines for astroglia (1321N1) neurons (SHSY5Y, differentiated retinoic acid) were used monitor changes transcript AQPs (AQP0 AQP12) response inflammation (simulated 10–100 ng/ml lipopolysaccharide [LPS], 24 h), hypoxia (5 min N2, followed by 0 h normoxia). AQP transcripts up-regulated both 1321N1 SHSY5Y included AQP0, AQP1 AQP11. Immunocytochemistry cells confirmed expression plasma membrane endoplasmic reticulum; increased 10-fold after LPS 0.3-fold. cells, 0.2-fold LPS; showed no appreciable change. Proposed peroxiporin roles tested using melondialdehyde (MDA) assays quantify lipid peroxidation brief H2O2. Boosting pretreatment lowered subsequent H2O2-induced MDA responses (∼50%) compared controls; conversely small interfering RNA knockdown (∼17%) H2O2, a similar trend siRNA. Interventions increase native activity are promising as new approaches mitigate damage caused aging neurodegeneration.

Язык: Английский

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Ginkgolide B can alleviate spinal cord glymphatic system dysfunction and provide neuroprotection in painful diabetic neuropathy rats by inhibiting matrix metalloproteinase-9

Neuropharmacology, Год журнала: 2024, Номер 250, С. 109907 - 109907

Опубликована: Март 14, 2024

Язык: Английский

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Aquaporins: Gatekeepers of Fluid Dynamics in Traumatic Brain Injury

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6553 - 6553

Опубликована: Июнь 14, 2024

Aquaporins (AQPs), particularly AQP4, play a crucial role in regulating fluid dynamics the brain, impacting development and resolution of edema following traumatic brain injury (TBI). This review examines alterations AQP expression localization post-injury, exploring their effects on overall outcomes. We discuss underlying molecular mechanisms expression, highlighting potential therapeutic strategies to modulate function. These insights provide comprehensive understanding AQPs TBI suggest novel approaches for improving clinical outcomes through targeted interventions.

Язык: Английский

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Aquaporins: New players in breast cancer progression and treatment response

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Сен. 21, 2022

Aquaporins (AQPs) are a family of small transmembrane proteins that selectively transport water and other molecules ions following an osmotic gradient across cell plasma membranes. This enables them to regulate numerous functions including homeostasis, fat metabolism, proliferation, migration, adhesion. Previous structural functional studies highlight strong biological relationship between AQP protein expression, localization, key in normal cancer tissues, where aberrant expression correlates with tumorigenesis metastasis. In this review, we discuss the roles AQP1, AQP3, AQP4, AQP5, AQP7 breast progression metastasis, role AQPs tumor microenvironment, potential contributions stromal-derived epithelial-derived cancer. Emerging evidence identifies as predictors response therapy targets for increasing their sensitivity treatment. However, these have not evaluated requirements structure on function within context We also examine how contribute patient’s treatment, existing inhibitors could serve novel predictive biomarkers Future should evaluate redundancy compensation mechanisms used overcome function. review highlights need additional research into molecularly therapeutic resistance by altering microenvironment.

Язык: Английский

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A review on contemporary nanomaterial-based therapeutics for the treatment of diabetic foot ulcers (DFUs) with special reference to the Indian scenario

Nanoscale Advances, Год журнала: 2022, Номер 4(11), С. 2367 - 2398

Опубликована: Янв. 1, 2022

Nanomaterial-based therapeutic treatment shows promising results in enhancing the anti-inflammatory, antimicrobial and angiogenic potential diabetic rodents for effective wound healing process.

Язык: Английский

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Modulating the Antioxidant Response for Better Oxidative Stress-Inducing Therapies: How to Take Advantage of Two Sides of the Same Medal?

Biomedicines, Год журнала: 2022, Номер 10(4), С. 823 - 823

Опубликована: Март 31, 2022

Oxidative stress-inducing therapies are characterized as a specific treatment that involves the production of reactive oxygen and nitrogen species (RONS) by external or internal sources. To protect cells against oxidative stress, have evolved strong antioxidant defense system to either prevent RONS formation scavenge them. The maintenance redox balance ensures signal transduction, development, cell proliferation, regulation mechanisms death, among others. stress can beneficially be used treat several diseases such neurodegenerative disorders, heart disease, cancer, other regulating system. Understanding various endogenous systems increase therapeutic efficacy stress-based therapies, leading clinical success in medical treatment. This review deals with recent novel findings cellular responses behind highlighting their implication human diseases, ulcers, skin pathologies, oncology, viral infections SARS-CoV-2.

Язык: Английский

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Aquaporin regulates cell rounding through vacuole formation during endothelial-to-hematopoietic transition

Development, Год журнала: 2023, Номер 150(11)

Опубликована: Июнь 1, 2023

ABSTRACT Endothelial-to-hematopoietic transition (EHT) is crucial for hematopoietic stem cell (HSC) generation. During EHT, the morphology of hemogenic endothelial cells (HECs) changes from flat and adherent to spherical cells, which detach dorsal aorta. HECs attain a rounded shape in mitosis-independent manner before adhesion termination, suggesting an atypical cell-rounding mechanism. However, direct mechanisms underlying this change during EHT remain unclear. Here, we show that large vacuoles were transiently formed avian HECs, aquaporin 1 (AQP1) was localized vacuole plasma membranes. Overexpression AQP1 non-HECs induced ectopic expansion, rounding subsequent detachment endothelium into bloodstream, mimicking EHT. Loss redundant AQP functions by CRISPR/Cas9 gene editing impeded morphological Our findings provide first evidence indicate segregation regulated water influx vacuoles. These important insights further exploration cell/tissue morphogenesis through water-adoptive cellular responses.

Язык: Английский

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Understanding molecular mechanisms and miRNA-based targets in diabetes foot ulcers

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Янв. 6, 2024

Язык: Английский

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