Nitric oxide, a ubiquitous molecule found throughout the natural world, is a key molecule implicated in many central and benefic molecular pathways and has a well-established role in the function of the central nervous system, as numerous studies have previously shown. Dysregulation of its metabolism, mainly the upregulation of nitric oxide production, has been proposed as a trigger and/or aggravator for many neurological affections. Increasing evidence supports the implication of this molecule in prevalent neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis. The mechanisms proposed for its neurotoxicity mainly center around the increased quantities of nitric oxide that are produced in the brain, their cause, and, most importantly, the pathological metabolic cascades created. These cascades lead to the formation of neuronal toxic substances that impair the neurons' function and structure on multiple levels. The purpose of this review is to present the main causes of increased pathological production, as well as the most important pathophysiological mechanisms triggered by nitric oxide, mechanisms that could help explain a part of the complex picture of neurodegenerative diseases and help develop targeted therapies.
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http://dx.doi.org/10.3390/antiox12030753 | DOI Listing |
Cells
January 2025
Institute of Anatomy & Cell Biology, Faculty of Medicine, Justus-Liebig-University, Aulweg 123, 35392 Giessen, Germany.
Vascular smooth muscle cell (SMC) relaxation by guanylyl cyclases (GCs) and cGMP is mediated by NO and its receptor soluble GC (sGC) or natriuretic peptides (NPs) ANP/BNP and CNP with the receptors GC-A and GC-B, respectively. It is commonly accepted that cultured SMCs differ from those in intact vessels. Nevertheless, cell culture often remains the first step for signaling investigations and drug testing.
View Article and Find Full Text PDFCells
December 2024
Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany.
Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture.
View Article and Find Full Text PDFJ Hypertens
December 2024
Institute for Fetology, The First Affiliated Hospital of Soochow University, Jiangsu.
Background: Paternal preconception alcohol exposure affects fetal development; however, it is largely unknown about the influences on offspring vasculature and mechanisms.
Methods: Offspring born form paternal rats treated with alcohol or water before pregnant was raised until 3 months of age. Vessel tone of mesenteric arteries was detected using myograph system; whole-cell calcium channel current in smooth muscle cells was tested using patch-clamp; molecule expressions were detected with real-time PCR, western blotting, and Dihydroethidium (DHE); DNA methylations were determined using targeted bisulfate sequencing assay.
J Am Heart Assoc
January 2025
Division of Cardiovascular Science, Faculty of Biology, Medicine and Health The University of Manchester Manchester UK.
Background: Heart failure with preserved ejection fraction (HFpEF) is linked to prolonged endoplasmic reticulum (ER) stress. P21-activated kinase 2 (Pak2) facilitates a protective ER stress response. This study explores the mechanism and role of Pak2 in HFpEF pathology.
View Article and Find Full Text PDFSmall
January 2025
Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, and Guangdong-Hong Kong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Diabetic ulcers (DUs) are characterized by a microenvironment with high oxidative stress, high blood glucose levels, and recalcitrant bacterial infections. This microenvironment is accompanied by long-term suppression of endogenous antioxidant systems, which makes their clinical management extremely challenging. To address this issue, a hybridized novel gold-palladium (AuPd) nanoshell of the injectable/injectable hydrogel system UiO/AuPd/BNN6/PEG@Gel (UAPsBP@Gel) is developed.
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