Objectives: Oxidative stress (OS), is defined as an imbalance of pro- and antioxidants, leading to increased production of free radicals, which can lead to cell damage and death, has been postulated as important factors in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Most research has concentrated on the antioxidant system, for the first time, this proof of concept study examines the prooxidant system by investigating kinetic parameters of the free radical producing enzyme xanthine oxidase directly in post mortem brain tissue.
Methods: We determined the Michaelis-Menten constant (K(M)) and the maximal velocity (V(Max)) of xanthine oxidase (XO) in the cortico-limbic system of patients with AD using activity assays.
Results: We found the Michaelis-Menton constant of XO significantly decreased in hippocampus of patients with AD compared to controls. None of the other brain regions showed any significant alterations of these parameters.
Conclusions: These results add further evidence to the amount of research indicating that OS plays an important role in AD. Moreover, these results should encourage more research in this field and it maybe speculated that this might open new avenues for treatment and prevention in AD.
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http://dx.doi.org/10.3109/15622971003728014 | DOI Listing |
BMC Med
December 2024
Department of Primary and Community Care, Radboud University Medical Centre, Radboud Institute for Health Sciences, Geert Grooteplein 10, Nijmegen, 6500HB, the Netherlands.
Background: Palliative sedation involves the intentional proportional lowering of the level of consciousness in patients with life-limiting disease who are experiencing refractory suffering. The efficacy of palliative sedation needs to be monitored to ensure patient comfort. The aim of this study was to evaluate the efficacy using discomfort levels combined with sedation/agitation levels.
View Article and Find Full Text PDFCell Commun Signal
December 2024
Department of Pharmacology, Physiology & Neuroscience New Jersey Medical School, The State University of New Jersey, Rutgers, Newark, NJ, USA.
Cell Mol Immunol
January 2025
Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
Microglia dysfunction-associated neuroinflammation is an important driver of Alzheimer's disease (AD), but the mechanism is poorly understood. Here, we show that demyelination promotes neuroinflammation and cognitive impairment via the lysophosphatidylserine (LysoPS)-GPR34 axis in AD. Demyelination is observed at the early stage and is accompanied by an increase in LysoPS in myelin debris in a 5xFAD mouse model of AD.
View Article and Find Full Text PDFJ Neurosci
December 2024
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis IN, USA
Anti-Aβ immunotherapy use to treat Alzheimer's disease is on the rise. While anti-Aβ antibodies provide hope in targeting Aβ plaques in the brain there still remains a lack of understanding regarding the cellular responses to these antibodies in the brain. In this study we sought to identify acute effects of anti-Aβ antibody on immune responses.
View Article and Find Full Text PDFIn Vivo
December 2024
Doctoral School of Biomedical Sciences, University of Oradea, Oradea, Romania.
Background/aim: Alzheimer's disease is a complex, incurable to date, multifactorial disease, which suggests the need for continued development of pharmacotherapy.
Materials And Methods: A comprehensive literature search was conducted to identify known ligands with anticholinesterase activity, resulting in the discovery of over 100 alkaloids that are also available in the PubChem database. Subsequently, the ligands underwent molecular docking to evaluate their affinity for the target enzyme.
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